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Calliandra portoricensis (C. portoricensis) is used in herbal homes in Nigeria to manage breast diseases. We investigated the anti-tumourigenic effects of chloroform extract of C. portoricensis (CP) in breast experimental cancer induced by N-methyl-N-nitrosourea (NMU) and benzo-(a)-pyrene (BaP). Fifty-six female rats were assigned into seven equal groups: Group 1 served as control, group 2 received NMU and BaP (50 mg/kg, each), groups 3 and 4 received [NMU + BaP] and treated with CP at 50 and 100 mg/kg, respectively. Group 5 received CP (100 mg/kg), group 6 received [NMU + BaP] and vincristine (0.5 mg/kg), while group 7 received vincristine (0.5 mg/kg). The NMU and BaP (i.p) were dissolved in normal saline and corn oil, respectively. The CP (oral) and vincristine (i.p) were given thrice and twice per week, respectively for 10 weeks. The [NMU + BaP] intoxication significantly decreased body weight gain by 32% while organo-somatic weight of mammary gland increased by 37%. Also, [NMU + BaP] decreased the activities of mammary catalase, glutathione-s-transferase, glutathione peroxidase, superoxide dismutase and total sulphurhydryl by 34%, 31%, 35%, 35% and 33%, respectively. The [NMU + BaP] increased inflammatory and oxidative stress markers; nitrite, lipid peroxidation and myeloperoxidase by 62%, 57% and 361%, respectively. Strong expression of BCL-2, IL-6, COX 2, β-catenin and iNOS in [NMU + BaP]-administered rats were observed. Histology revealed glands with malignant epithelial cells and high nucleocytoplasm in [NMU + BaP] rats. Treatment with CP attenuated inflammation, apoptosis and restored cyto-architecture of mammary gland. Overall, CP abates mammary tumourigenesis by targeting cellular pathways of inflammation and apoptosis.

Zearalenone (ZEN) is a mycotoxin that contaminates crops worldwide and whose toxic adverse effects are well documented. This study aims to evaluate the protective effect of gallic acid (GA) against biochemical, oxidative, inflammatory, and pathological changes in ZEN treated rats’ hepatorenal system. Wistar rats (n = 50; 150 ± 30 g) were randomly grouped into five cohorts (= 10) specifically: Control (rat chow); ZEN alone (100 µg/kg; per os), GA alone (40 mg/kg; per os), ZEN + GA1 (100 µg/kg + 20 mg/kg per os) and ZEN + GA2 (100 µg/kg + 40 mg/kg per os) and the study was for 28 successive days. Upon terminal sacrifice, biomarkers of hepatorenal function and oxidative stress were analyzed. An assessment of cytokine levels (IL-1β, IL-10) and histopathology of the liver and kidneys was also performed. Relative to the control, serum levels of urea, creatinine, and hepatic transaminases increased significantly (p

Anaerobic codigestion (AcD) of agroindustrial residues was investigated. Granular sludge from bench-scale bioreactors digesting different manure were acclimated and recycled as microbial seed sludge to demonstrate inoculum-type influence on digestion performance. The biomethane potential (BMP) assay was operated for 30 days at 40 ± 2 °C in batch-type laboratory-scale reactors (100 mL). In inoculum amended reactors, codigestion showed significant, yet distinctive, biomethanation than monodigestion with a 5-fold increase (p

Benzo-a-pyrene (BaP) exposure is toxic to the reproductive systems. The beneficial effects of taurine (TAU) against BaP-induced toxicity in the epididymis and testes of rats co-treated with BaP (10 mg/kg) and TAU at doses of 100 and 200 mg/kg for 28 successive days are reported in this study. Co-treatment with TAU significantly alleviated BaP-induced decreases in sperm quality, reproductive hormones, oxidative stress and inflammatory biomarkers. TAU also lessened epididymal and testicular injuries in rats. TAU ameliorated toxic responses in the epididymis and testes of rats exposed to BaP by abating oxidative and inflammatory responses, improved sperm quality and enhanced reproductive hormone levels.

Petroleum product fumes (PPFs) containing toxic organic components are pervasive in the environment, emanating from anthropogenic activities, including petroleum exploration and utilization by end-user activities from petrol–gasoline stations. Petrol station attendants are exposed to PPF through inhalation and dermal contact with consequent toxicological implications. We investigated the effects of chronic exposure (60 and 90 days) to petrol (P), kerosene (K) and diesel (D) alone and combined exposure to petrol, kerosene and diesel (PKD) fumes on hepatotoxicity, haematological function and oxidative stress in rats. Following sacrifice, we evaluated hepatic damage biomarkers, blood glucose, oxidative stress and haematological function. Chronic exposure to PPF significantly increased organo-somatic indices, blood glucose, biomarkers of hepatic toxicity and oxidative stress in an exposure duration-dependent manner. There was a simultaneous decrease in the protective capacity of antioxidants. Furthermore, exposure to PPF increased pro-inflammatory biomarkers in rats (90 > 60 days). Regardless of exposure duration, plateletcrit, mean platelet volume, platelet distribution width and red cell distribution width in the coefficient of variation increased, whereas red blood cell count, haemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, white blood cell, lymphocyte, monocyte–basophil–eosinophil mixed counts and platelet count decreased after 60 and 90 days exposure. Microscopic examination of the liver demonstrated hepatic pathological changes paralleling the duration of exposure to PKD fumes. However, the injury observed was lesser to that of rats treated with the diethylnitrosamine – positive control. Our results expanded previous findings and further demonstrated the probable adverse effect on populations’ health occasioned by persistent exposure to PPF. Individuals chronically exposed by occupation to PPF may be at greater risk of developing disorders promoted by continuous oxido-inflammatory perturbation and suboptimal haematological–immunologic function – thereby enabling a permissive environment for pathogenesis notwithstanding the limitation of quantifying PPF absolute values in our model system.

Furan formed in processed food is hepatotoxic and likely carcinogenic in humans. We investigated protocatechuic acid (PCA) protective role in rats' hepatorenal function treated with furan. Rats were grouped and treated as follows: Control, PCA (50 mg/kg), furan alone (8 mg/kg), furan + PCA1 (25 + 8 mg/kg), and furan + PCA2 (50 + 8 mg/kg). Upon sacrifice, evaluation of hepatorenal function, oxidative stress status, reactive oxygen and nitrogen species (RONS), lipid peroxidation (LPO), myeloperoxidase (MPO) activity, among nitric oxide (NO) levels were performed. Cytokine levels (IL-10, IL-1ß, TNF-alpha), Caspase 3 and 9 activities, and histopathological examination were also assessed. We found that the final body and relative liver weights changed significantly

Plant-derived phenolics are utilized as chemopreventive agents to abate adverse toxic responses associated with drug-induced damages. Tamoxifen (TAM)—a chemotherapeutic agent—is used in managing all stages of hormone-dependent breast cancer. Notwithstanding TAM’s clinical side effect—including hepatic toxicity—its use is commonplace. The present study investigates the effect of Chlorogenic acid (CGA: 25 and 50 mg kg−1; per os (p.o)) reported to exhibit various beneficial properties, including antioxidative effect against TAM (50 mg/kg; p.o.)-induced hepatorenal toxicities in rats treated as follows: Control, CGA, or TAM alone, and rats co-treated with CGA and TAM for 2 weeks. Biomarkers of hepatorenal function, oxido-inflammatory stress, and hepatorenal histopathology were performed. We observed that TAM alone decreased relative organ weights (ROW), marginally impacted rat’s survivability, and significantly (P

A study of the environmental degradation of the activities of illegal refineries on the mangrove ecosystem was carried out at Escravos the study area and its located in Warri South Local Government Area of Delta State and plays host to two major transnational oil companies Shell and Chevron. In achieving the study’s objective, samples of water and sediments were collected from both remediated and impacted sites to test for heavy metal, Total Petroleum Hydrocarbon (TPH) and Polycyclic Aromatic Hydrocarbon (PAH). The extraction of TPH and PAH from soil was accomplished through the technique of Soxhlet method while the atomic-absorption spectrophotometry method was used to determine the presence of heavy metals. The study showed that TPH concentrations appears in the following order of RS1 > RS3 > RS2 > RS1 with the TPH in the impacted sediment were relatively higher than the values recorded for the remediated sediment. The order of abundance of metal concentration in this study is Fe > Zn >Mn>Pb> Cu > Cd and Ni. Data from this study further reveals that the net concentration of the metals investigated for both seasons show that all the metals investigated in the dry season are higher than those from the raining season. The concentrations of PAHs in this study were higher in the sediments than in the water samples.

This study was carried out to predict the source of the sixteen priority polycyclic aromatic hydrocarbon (PAH) compounds in water, sediment, and biota samples from River Ethiope, Delta State, Southern Nigeria. The samples were extracted using soxhlet extraction and analysed with GC/FID. Results obtained for total concentration of the sixteen priority PAHs ranges from 0.185 to 3.679 mg/kg (sediment), 0.000 to 27.353 µg/l (water), and 0.053 to 6.060 µg/kg (biota samples). The result indicated that the concentration level in the water, sediment, and biota are considerably low. Although the PAH were below the USEPA standard, the observed levels can cause adverse effects for lower dwelling aquatic organisms, which are exposed to the sediments daily. Therefore, persistent monitoring and strict adherence to responsible waste discharge should be upheld by all manufacturing and agro-industries in the catchment of the river to avoid deleterious effects on biodiversity and to ensure the safety of the consumers. From the source prediction, the results obtained show the sources are quite similar across the sample sites. This is an indication that the PAHs in the water samples are mostly of pyrogenic origin, except the water samples from Abraka site 2, which are petrogenic. All river sediment samples show pyrogenic origins. Keywords: Source prediction, polycyclic aromatic hydrocarbons (PAHs), combustion, River Ethiope.

Garcinia kola seed is used to manage liver diseases in ethnomedicine. However, there is limited information on its role in Cisplatin (CIS)-induced toxicity. Here, we investigated the potential of h...

Reproductive toxicity associated with excessive exposure to multi-walled carbon nanotubes (MWCNTs), which are commonly used in medicine as valuable drug delivery systems, is well documented. Kolaviron, a bioflavonoid isolated from Garcinia kola seeds, elicits numerous health beneficial effects related to its anti-inflammatory, anti-genotoxic activities, anti-apoptotic, and antioxidant properties. However, information on the role of kolaviron in MWCNTs-induced reproductive toxicity is not available in the literature. Herein, we assessed the protective effects of kolaviron on MWCNTs-induced dysfunctional reproductive axis in rats following exposure to MWCNTs (1 mg/kg) and concurrent treatment with kolaviron (50 or 100 mg/kg body weight) for 15 successive days. Results showed that MWCNTs-induced dysfunctional reproductive axis as evidenced by deficits in pituitary and testicular hormones, marker enzymes of testicular function, and sperm functional characteristics were abrogated in rats co-administered with kolaviron. Moreover, co-administration of kolaviron-abated MWCNTs-induced inhibition of antioxidant enzyme activities increases in oxidative stress and inflammatory indices. This is evidenced by diminished levels of tumor necrosis factor-alpha, nitric oxide, lipid peroxidation, reactive oxygen, and nitrogen species as well as reduced activity of myeloperoxidase in testes, epididymis, and hypothalamus of the rats. Biochemical data on the chemoprotection of MWCNTs-induced reproductive toxicity were corroborated by histological findings. Taken together, kolaviron suppressed dysfunctional reproductive axis associated with MWCNTs exposure via abrogation of oxidative stress and inflammation in male rats.

Reproductive dysfunction stemming from chemical agents may lead to infertility. We examined the protective effects of Calliandra portoricensis ( CP) extract on benzo[a]pyrene (BaP) and N-methyl- N-nitrosourea (NMU)-induced ovarian and uterine toxicity in rat, treated as follows: control (group 1), NMU + BaP (group 2), groups 3 and 4 received (NMU + BaP), and CP (50 and 100 mg/kg), respectively. Group 5: CP (100 mg/kg) alone, group 6: (NMU + BaP) and vincristine (VIN: 0.5 mg/kg) and group 7: VIN alone. Rats were injected at age 7, 10, and 13 weeks with single doses of NMU and BaP for 10 consecutive weeks. NMU + BaP significantly ( P Impact statementInfertility resulting from reproductive impairment is traumatic in families. Exposure to chemicals may play insidious roles not easily connected to infertility. We examined benzo[a]pyrene (BaP), and N-methyl nitrosourea (NMU)-induced ovarian and uterine toxicity and the role of Calliandra portoricensis in mitigating toxicity. In a bid to illuminate folk medical claims cloaked in mystery, unearthing lost knowledge, advance natural chemopreventive agents, and report new evidence lacking in the literature attributed to CP. Although CP is known to exhibit anticonvulsant, antidiarrheal, antipyretic, antirheumatic, and analgesic effects in humans, its possible roles for mitigating toxicity stemming from inadvertent chemical exposures are reported here. Our findings affirm and further show that CP abates toxic response incumbent on oxidative damage and inflammatory responses associated with NMU and BaP exposure. Development of phytochemical derived from CP may serve as a potential natural therapy against chemical toxicities in individuals inadvertently exposed, and promote human health and reproductive satiety.

Seasonal trends of polycyclic aromatic hydrocarbon in the sediment of River Ethiope in Delta State, Southern Nigeria were assessed in this study. Samples were taken from six different points at Ethiope River along its banks during the dry and rainy seasons. Samples were extracted using soxhlet apparatus and analysed with gas chromatography-flame ionization detector (GC/FID). The results obtained for the PAHs concentration ranges from 184.73 µg/kg – 3679.13 µg/kg for dry season and for rainy season, some stations were below detection limit (BDL) to a maximum value of 693.43 µg/kg. The result clearly shows that the total concentration of polycyclic aromatic hydrocarbon detected in the dry season was higher than those of the rainy season. Similarly, more PAHs compound of higher and lower rings were found in the dry season than in the rainy season in sediment samples. Although, the PAHs concentrations were quite low which indicated no danger status from the consumption or dermal contact for humans’ point of view, however, the levels can cause adverse effects for lower aquatic organisms which are exposed to the sediments on a daily basis. Therefore, persistent monitoring and strict adherence to responsible waste discharge should be upheld by all manufacturing and agro industries located in the study area in order to avoid deleterious effects of the biodiversity in the water bodies as well as ensuring safety of the consumers.

Exposure to multi-walled carbon nanotubes (MWCNTs) reportedly elicits neurotoxic effects. Kolaviron is a phytochemical with several pharmacological effects namely anti-oxidant, anti-inflammatory, and anti-genotoxic activities. The present study evaluated the neuroprotective mechanism of kolaviron in rats intraperitoneally injected with MWCNTs alone at 1 mg/kg body weight or orally co-administered with kolaviron at 50 and 100 mg/kg body weight for 15 consecutive days. Following exposure, neurobehavioral analysis using video-tracking software during trial in a novel environment indicated that co-administration of both doses of kolaviron significantly (p

As gallic acid (GA) role in zearalenone (ZEN); mediated reproductive dysfunction has not been studied, we report on GA's effect on reproductive dysfunction in rats treated with ZEN-100 µg/kg alone, or with GA-40 mg/kg; for 4 weeks. The mycotoxin ZEN contaminates crops, causing toxicity on ingestion, economic losses, and alters reproductive function. Relative to control, GA reversed ZEN-induced reduction of rats' testicular function enzymes and reproductive hormones and improved ZEN-impaired sperm quality. GA significantly (p

Objectives Diethylnitrosamine (DEN) is found in workplaces, processed meats, tobacco smoke, whiskey, etc. It is capable of forming DNA-adducts. Fluted pumpkin (Telfairia occidentalis [To]) is a medicinal plant, and its herbal preparations have been employed variously in ethnomedicine. Furthermore, it has been reported to possess anti-oxidant, anti-cancer, anti-inflammatory properties. We investigated the possible mitigating effect of the leaf paste of To on DEN-induced deleterious effects in male Wistar rats. Methods Forty-five rats weighing between 100 and 150 g were equally divided into nine groups and treated thus: Group 1 (negative control), Group 2 (0.05 mg/kg carboxymethyl cellulose [CMC] daily), Group 3 (positive control, 25 mg/kg bw DEN administered intraperitoneally thrice per week), Group 4 (25 mg/kg bw quercetin [QUE] daily alone), Groups 5 and 6 (100 and 200 mg/kg bw To daily, respectively), Group 7 (25 mg/kg bw DEN and QUE), Groups 8 and 9 (25 mg/kg bw DEN with 100 and 200 mg/kg bw To, respectively). Blood glucose levels, liver damage biomarkers (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and gamma-glutamyltransferase [γ-GT]), frequency of micronucleated polychromatic erythrocyte (mPCEs), and liver histology were assessed. Results DEN significantly (pTo by ameliorating the adverse effects caused by DEN. Conclusions Taken together, the leaf paste of To is capable of mitigating DEN-induced hepatotoxicity and clastogenicity in male Wistar rats.

We examined the individual and combined effect of 3-Indolepropionic acid (IPA) and Chlorpyrifos (CPF) on rat hepatorenal function. The experimental cohorts (n=6) were treated per os for 14 consecutive days as follows: Control (Corn oil 2 mL/kg body weight), CPF alone (5 mg/kg), IPA alone (50 mg/kg) and the co-treated cohorts (CPF: 5 mg/kg + IPA: 25 or 50 mg/kg). Biomarkers of hepatorenal damage, antioxidant and myeloperoxidase (MPO) activities, the levels of nitric oxide (NO), lipid peroxidation (LPO) and reactive oxygen and nitrogen (RONS) species were spectrophotometrically evaluated. Besides, the concentration of tumour necrosis factor-alpha (TNF- α), interleukin-1 β (IL-1β) and caspase-3 activity and 8-hydroxy-2’-deoxyguanosine adducts (8-OHdG) was also assessed by Enzyme-Linked Immunosorbent Assay. Treatment with CPF alone increased biomarkers of hepatorenal toxicity was significantly (p) alleviated in rats co-exposed to CPF and IPA. Moreover, the decrease in antioxidant status as antioxidant elevation in RONS and LPO were lessened (p) in rats co-treated with CPF and IPA. CPF mediated increases in TNF-α, IL-1β, NO, MPO and caspase-3 activity were reduced (p) in the liver and kidney of rats co-exposed to CPF and IPA. In addition, 8-OHdG adducts formation were reduced in rats treated with 3-IPA dose-dependently. Light microscopic examination showed that histopathological lesions severity induced by CPF were alleviated in rats co-exposed to IPA and CPF. In conclusion, the results demonstrated that rats co-exposed to IPA and CPF exhibited reduced CPF-induced oxidative stress, inflammation, DNA damage and caspase-3 activation of the liver and kidney.

We examined the effect of 3-Indolepropionic acid (3-IPA), an antioxidant on the organophosphorus pesticide chlorpyrifos (CPF)-induced reproductive toxicity in rats. The five experimental rat cohorts were treated per os for 14 consecutive days as follows: Control (Corn oil 2 mL/kg body weight), CPF alone (5 mg/kg), 3-IPA alone (40 mg/kg) and the co-treated rat cohorts (CPF:5 mg/kg + 3-IPA: 20 or 40 mg/kg). Biomarkers of testicular and epididymal function, oxidative stress, myeloperoxidase (MPO) activity and the levels of nitric oxide (NO), reactive oxygen and nitrogen (RONS) species and lipid peroxidation (LPO) were assessed. Also, tumour necrosis factor-alpha (TNF-α), Bcl-2-associated X (Bax) and B cell lymphoma 2 (Bcl-2) proteins were estimated, and tissue histology was microscopically examined. CPF alone significantly (p0.05) increased biomarkers of reproductive toxicities were averted in rats co-treated 3-IPA. Decreases in antioxidants and increases in lipid peroxidation and reactive oxygen and nitrogen species were lessened (p0.05) in CPF and 3-IPA co-treated rats. CPF mediated increases in TNF-α, NO, Bax, and MPO activity was reduced (p0.05) in the epididymis, testes, and hypothalamus of rats co-treated with 3-IPA. In addition, Bcl-2 expression was increased in rats co-treated with 3-IPA dose-dependently. Histopathological examination revealed severe lesions induced by CPF were prevented in rats co-treated with 3-IPA. Our findings demonstrate that exogenous 3-IPA reduced CPF-induced oxidative stress, inflammation, and apoptosis in the epididymis and testes of male rats.

We assessed the individual and combined consequence of 3-indolepropionic acid on aflatoxin B1-induced reproductive toxicity in rats. The experimental cohorts were dosed for four consecutive weeks with aflatoxin B1 (50 μg/kg), 3-indolepropionic acid (50 mg/kg), and both (aflatoxin B1: 50 μg/kg + 3-indolepropionic acid: 25 or 50 mg/kg), and the untreated control. Following sacrifice, biomarkers of testicular, epididymal and hypothalamic oxidative status, lipid peroxidation, reactive oxygen and nitrogen species, nitric oxide levels and myeloperoxidase activity were determined. Besides, tumour necrosis factor-alpha, Bcl-2 and Bax proteins were also assessed. Aflatoxin B1-induced testicular, epididymal and hypothalamic oxidative stress was significantly alleviated with 3-indolepropionic acid co-treatment. Also, increases in biomarkers of oxidative stress and reduced levels of antioxidants were abated significantly in rats co-treated with 3-indolepropionic acid. Aflatoxin B1-mediated increase in tumour necrosis factor-alpha, Bax, nitric oxide and myeloperoxidase activity in the examined organs was decreased significantly in aflatoxin B1 and 3-indolepropionic acid co-treated rats. Also, 3-indolepropionic acid dose dependently reduced Bcl-2 levels in the treated rats. The degree of aflatoxin B1-induced histopathological injuries was minimised in rats co-treated with 3-indolepropionic acid. Our results demonstrated that 3-indolepropionic acid protected experimental rats from aflatoxin B1-induced oxido-inflammatory stress and apoptotic response in the examined organs.

Doxorubicin (DOX) is a chemotherapeutic drug used in the treatment of various cancer types. DOX toxic side effects include neuronopathy and memory deficits. We investigated the effect of the antioxidant luteolin (LUT: 50 or 100 mg/kg; per os) on DOX (2 mg/kg; intraperitoneal)-induced oxidative stress (OS), inflammation, and apoptosis in the brain of Wistar rats for 14 days. We observed that LUT reduced DOX-mediated increase in OS biomarkers-catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase. LUT increased glutathione and total sulphydryl levels and alleviated DOX-induced increases in the levels of reactive oxygen and nitrogen species, lipid peroxidation, myeloperoxidase, nitric oxide, tumor necrosis factor-α, and interleukin-1β (IL-1β). Additionally, LUT suppressed caspase-3 activity, increased anti-inflammatory cytokine-IL-10 level, and reduced pathological lesions in the examined organs of rats cotreated with LUT and DOX. Collectively, cotreatment with LUT lessened DOX-induced neurotoxicity. Supplementation of LUT as a chemopreventive agent might be useful in patients undergoing DOX chemotherapy.

The present study examined the influence of co-exposure to cadmium (Cd) and nickel (Ni) on hepatorenal function as well as the protective role of omega-3 polyunsaturated fatty acids (ω-3FA) in rats. The animals were exposed to Cd (5 mg/kg) and Ni (150 μg/L in drinking water) singly or co-exposed to both metals and ω-3FA at 20 mg/kg for 14 consecutive days. Results showed that hepatorenal injury resulting from individual exposure to Cd or Ni was not aggravated in the co-exposure group. Moreover, ω-3FA markedly abrogated the reduction in the antioxidant enzyme activities, the increase in reactive oxygen and nitrogen species, and lipid peroxidation induced by Cd and Ni co-exposure. Additionally, ω-3FA administration markedly suppressed the increase in hepatic and renal myeloperoxidase activity, nitric oxide, tumor necrosis factor alpha, and interleukin-1 β levels in the co-exposure group. Genotoxicity resulting from individual exposure to Cd or Ni was intensified in the co-exposure group. However, ω-3FA administration markedly ameliorated the genotoxicity and histological lesions in the co-exposure group. Taken together, co-exposure to Cd and Ni aggravated genotoxicity and not oxido-inflammatory stress in the liver and kidney of rats. ω-3FA abated hepatorenal injury and genotoxicity induced by Cd and Ni co-exposure in rats.

Ethnopharmacological relevance Apoptosis is downregulated in all forms of cancers. The mitochondrion has been implicated in the apoptotic process and, recently has been targeted in cancer therapy because of its role in cancer progression. Medicinal plants are used in the treatment of cancer, in particular, Calliandra portoricensis (CP) in the management of prostate cancer in Nigeria ethnomedicine. Aim of the study This study was designed to investigate the effects of CP on mitochondrial-mediated apoptosis and cell proliferation using prostate cancer cells. Materials and methods Prostatic LNCaP, DU-145, lung adenocarcinoma and healthy VERO cells were used to assess cell proliferation. Cell cycle analysis was evaluated by flow cytometry. Levels of pro-apoptotic Bax, anti-apoptotic Bcl-2, Cytochrome C Release (CCR) and activation of caspases 3(C3) and 9 (C9) were determined by ELISA, while mitochondrial integrity was evaluated by Fluorescent Intensity Ratio (FIR). Results Methanol Fraction of C. portoricensis (MFCP) inhibited proliferation of prostatic LNCaP, DU-145, lung adenocarcinoma and healthy VERO cells with IC50 values of 2.4 ± 0.2, 3.3 ± 0.2, 3.6 ± 0.2 and 17.9 ± 1.6 µg/mL, respectively. The growth inhibition by MFCP correlated with a 3-fold decreased expression of Bcl-2 and a 4-fold increase in Bax levels at 10 µg/mL in LNCaP cells. Furthermore, MFCP caused a 3.5-fold reduction in FIR at 10 µg/mL and induced CCR by 4.2 folds at the same concentration relative to control. The MFCP-induced CCR is associated with activation of C3 and C9 at 10 µg/mL by 4.2 and 5.1 folds, respectively which prompted cancer cells to arrest at S phase. The LC-MS analysis revealed the presence of polyphenols including gallic acid and afzelechin in MFCP. Conclusion Taken together, MFCP- induced cell death is mediated by alteration of mitochondrial integrity and cell cycle arrest. Hence, methanol fraction of C. portoricensis may be effective for cancer pharmacotherapy.

Ethnopharmacological relevance Calliandra portoricensis (CP) is a herb widely used in Nigeria for the treatment of breast engorgement. However, the scientific evidence of this use and its mechanisms of action is not clearly understood. Aim of the study We assessed the chemopreventive effects of methanol extract of CP on N-methyl-N-nitrosourea (NMU)-induced mammary gland toxicity in rats. Materials and methods Fingerprinting of methanol extract of CP by Gas Chromatography-Mass Spectrometry (GC-MS) was done. Female Wistar rats were assigned into eight groups: Group 1 (control), group 2 received NMU only, groups 3, 4 and 5 received NMU and treated with CP at doses of 100, 200 and 300 mg/kg, respectively. Group 6 received CP (300 mg/kg), group 7 received NMU and vincristine, while group 8 received vincristine. Results The weight-gain by rats decreased in all groups that received NMU. Administration of NMU significantly increased organo-somatic weight of mammary gland by 52%. The NMU increased serum nitric oxide, total bilirubin, mammary myeloperoxidase and lipid peroxidation by 76%, 87%, 130% and 21%, respectively, as well as activities of serum aspartate aminotransferase and lactate dehydrogenase. Also, NMU-treated rats had decreased total sulphydryl, reduced glutathione and catalase. Immunohistochemistry revealed strong expression of estrogen, progesterone and EGFR-2 proteins in NMU-treated rats. Treatment with CP (200 and 300 mg/kg) attenuated NMU-induced inflammation and oxidative stress. Conclusion CP ameliorated NMU-induced toxicity by modulating different cellular targets.

Doxorubicin is an effective anti-neoplastic agent; the reported toxicities of DOX limit its use. Luteolin is a polyphenolic phytochemical that exhibits beneficial biological effects via several mechanisms. We investigate luteolin protective effects on hepatorenal toxicity associated with doxorubicin treatment in rats. For 2 weeks, randomly assigned rat cohorts were treated as follows: control, luteolin (100 mg/kg; per os), doxorubicin alone (2mg/kg; by intraperitoneal injection), co-treated cohorts received luteolin (50 and 100 mg/kg) in addition to doxorubicin. Treatment with doxorubicin alone significantly (p < 0.05) increased biomarkers of hepatorenal toxicities in the serum. Doxorubicin also reduced relative organ weights, antioxidant capacity, and anti-inflammatory cytokine interleukine-10. Doxorubicin also increased reactive oxygen and nitrogen species, lipid peroxidation, pro-inflammatory-interleukin-1β and tumour necrosis factor-α-cytokine, and apoptotic caspases-3 and -9). Morphological damage accompanied these biochemical alterations in the rat’s liver and kidney treated with doxorubicin alone. Luteolin co-treatment dose-dependently abated doxorubicin-mediated toxic responses, improved antioxidant capacity and interleukine-10 level. Luteolin reduced (p < 0.05) lipid peroxidation, caspases-3 and -9 activities and marginally improved rats’ survivability. Similarly, luteolin co-treated rats exhibited improvement in hepatorenal pathological lesions observed in rats treated with doxorubicin alone. In summary, luteolin co-treatment blocked doxorubicin-mediated hepatorenal injuries linked with pro-oxidative, inflammatory, and apoptotic mechanisms. Therefore, luteolin can act as a chemoprotective agent in abating toxicities associated with doxorubicin usage and improve its therapeutic efficacy.

Perfluorooctanoic acid is a synthetic perfluoroalkyl-persistent in the environment and toxic to humans. N-acetylcysteine is a pro-drug of both amino acid l-cysteine and glutathione-a non-enzymatic antioxidant. N-acetylcysteine serves as an antidote for paracetamol poisoning and alleviates cellular oxidative and inflammatory stressors. We investigated N-acetylcysteine role against reproductive toxicity in male Wistar rats (weight: 140-220 g; 10 weeks old) posed by perfluorooctanoic acid exposure. Randomised rat cohorts were dosed both with perfluorooctanoic acid (5 mg/kg; p.o) or co-dosed with N-acetylcysteine (25 and 50 mg/kg p.o) for 28 days. Sperm physiognomies, biomarkers of testicular function and reproductive hormones, oxidative stress and inflammation were evaluated. Co-treatment with N-acetylcysteine significantly (p < .05) reversed perfluorooctanoic acid-mediated decreases in reproductive enzyme activities, and adverse effect on testosterone, luteinising and follicle-stimulating hormone concentrations. N-acetylcysteine treatment alone, improved sperm motility, count and viability, and reduced total sperm abnormalities. Co-treatment with N-acetylcysteine mitigated perfluorooctanoic acid-induced alterations in sperm function parameters. N-acetylcysteine abated (p < .05) perfluorooctanoic acid-induced oxidative stress in experimental rats testes and epididymis, and generally improved antioxidant enzyme activities and cellular thiol levels. Furthermore, N-acetylcysteine suppressed inflammatory responses and remedied perfluorooctanoic acid-mediated histological injuries in rat. Cooperatively, N-acetylcysteine enhanced reproductive function in perfluorooctanoic acid dosed rats, by lessening oxidative and nitrative stressors and mitigated inflammatory responses in the examined organ.

The neurotoxic impact of dietary exposure to aflatoxin B1 (AFB1 ) is documented in experimental and epidemiological studies. Gallic acid (GA) is a triphenolic phytochemical with potent anticancer, anti-inflammatory, and antioxidant activities. There is a knowledge gap on the influence of GA on AFB1 -induced neurotoxicity. This study probed the influence of GA on neurobehavioral and biochemical abnormalities in rats orally treated with AFB1 per se (75 µg/kg body weight) or administered together with GA (20 and 40 mg/kg) for 28 uninterrupted days. Behavioral endpoints obtained with video-tracking software demonstrated significant (p < .05) abatement of AFB1 -induced anxiogenic-like behaviors (increased freezing, urination, and fecal bolus discharge), motor and locomotor inadequacies, namely increased negative geotaxis and diminished grip strength, absolute turn angle, total time mobile, body rotation, maximum speed, and total distance traveled by GA. The improvement of exploratory behavior in animals that received both AFB1 and GA was confirmed by track plots and heat maps appraisal. Abatement of AFB1 -induced decreases in acetylcholinesterase activity, antioxidant status and glutathione level by GA was accompanied by a marked reduction in oxidative stress markers in the cerebellum and cerebrum of rats. Additionally, GA treatment abrogated AFB1 -mediated decrease in interleukin-10 and elevation of inflammatory indices, namely tumor necrosis factor-α, myeloperoxidase activity, interleukin-1β, and nitric oxide. Further, GA treatment curtailed caspase-3 activation and histological injuries in the cerebral and cerebellar tissues. In conclusion, abatement of AFB1 -induced neurobehavioral abnormalities by GA involves anti-inflammatory, antioxidant, and antiapoptotic mechanisms in rats.

Toxicities linked with Benzo (a) pyrene B[a]P exposure, particularly in liver and kidney have been reported in both animals and humans. Taurine (2-aminoethane sulfonic acid) is an intracellular β-amino acid reported to elicit hepatorenal protective functions. However, the modulatory effect of taurine on hepatorenal toxicity associated with exposure to B[a]P has not been reported. This study evaluated the effects of taurine on the hepatorenal toxicities induced in cohorts of rats exposed to B[a]P. Experimental rats were treated as follows: B[a]P (10 mg/kg); co-treated cohorts –B[a]P (10 mg/kg) plus taurine (100 or 200 mg/kg) for 4 successive weeks. Results show that co-dosing with taurine significantly (P

Ingestion of perfluorooctanoic acid (PFOA) elicits toxicities in the hepatorenal system. We investigated the effect of PFOA and N-acetylcysteine (NAC) on the hepatorenal function of rats treated thus: control, PFOA (5 mg/kg), NAC (50 mg/kg), PFOA + NAC (5 and 25 mg/kg), and PFOA + NAC (5 and 50 mg/kg). We observed that NAC significantly (p0.05) reduced PFOA-induced increase in hepatic and renal function biomarkers of toxicities relative to PFOA alone and alleviated (p0.05) decreases in antioxidant status. Increases in oxidative stress and lipid peroxidation in PFOA-treated rats were reverted to normal by NAC and abated increased pro-inflammatory mediators, and decreased anti-inflammatory cytokine both in the hepatorenal system PFOA treated rats. Histology of the kidney and liver indicated that NAC, abated the severity of PFOA-induced damage significantly. Our findings affirm further that oxido-inflammatory mediators involved in PFOA-mediated toxicity can be effectively blocked by NAC through its antioxidant activity.

Doxorubicin (DOX), is a drug against lung malignancies with undesirable side effect including oxidative, inflammatory and apoptotic effects. Luteolin (LUT), present in fruits and vegetables is pharmacologically active against oxido-inflammatory and apoptotic responses. The present study examined the effect of LUT on DOX-induced lungs and blood dysfunction in Wistars rat (sex: male; 10 weeks old, 160 ± 5 g). Randomly grouped (n = 10) rats were treated as follows: control, LUT alone (100 mg/kg; per os), DOX (2 mg/kg; i. p), and co-treated rats with LUT (50 or 100 mg/kg) and DOX for two consecutive weeks. DOX alone adversely altered the final body and relative organ weights, red and white blood cell and platelet counts. DOX significantly (p > 0.05) reduced lungs antioxidant capacity, and anti-inflammatory cytokines; increased biomarkers of oxidative stress, caspase-3 activity, and pro-inflammatory cytokine. Morphological damages accompanied these biochemical alterations in the lung of experimental rats. Co-treatment with LUT, dose-dependently reversed DOX-mediated changes in rats' survival, toxic responses, and diminished oxidative stress in rat's lungs. Furthermore, co-treatment with LUT resulted in the reduction of pro-inflammatory cytokines and apoptotic biomarkers, increased red and white blood cell, platelet counts and abated pathological injuries in rat lungs treated with DOX alone. In essence, our findings indicate that LUT dose-dependently mitigated DOX-induced toxicities in the lungs and haematopoietic systems. Supplementation of patients on DOX-chemotherapy with phytochemicals exhibiting antioxidant activities, specifically LUT, could circumvent the onset of unintended toxic responses in the lungs and haematopoietic system exposed to DOX.

A new CuII complex (1) was synthesized by reacting 4-chlorobenzoic acid, benzimidazole and metal salt using ethanol&ndash, water (1:1 v/v) as a solvent at room temperature. The complex was characterized by single-crystal X-ray analysis, FTIR and UV&mdash, vis spectroscopy. A distorted square pyramidal geometry of the CuII center was observed from the single-crystal X-ray study, which also revealed that the uncoordinated oxygen atom of the carboxylate anions forms intermolecular hydrogen bonds with the N&ndash, H groups of the benzimidazole ligands. The Hirschfeld analysis results revealed that the molecular packing of 1 is mainly controlled by O&hellip, H (12.7%), Cl..H (16.4%), C...H (24.4%) and H...H (31.1%) contacts. Density functional theory (DFT) calculations were performed to compute the HOMO&ndash, LUMO energy gap and electrostatic potential map for the charge transfer regions within the molecule and identify the possible electrophilic and nucleophilic regions of the molecule. A number of reactivity parameters calculated on the basis of EHOMO and ELUMO show its significant polarizability and reactive nature. Complex 1 was also examined and screened for its potential antibacterial effect using the agar well diffusion method. The newly synthesized complex showed an effective and higher killing rate of the microbes in antibacterial testing compared to the parent ligand. The CuII complex (1) showed an enhanced inhibitory activity against P. aeruginosa and equally demonstrated greater binding affinity with DNA gyrase (1KIJ) compared to its ligands according to the molecular docking studies.

Reports over the years have demonstrated toxic side effect-including reproductive toxicity- of tamoxifen (TAM), a drug of choice in the management of primary breast cancer. Chlorogenic acid (CGA), a dietary polyphenol, reportedly elicits beneficial pharmacological effects. However, the impact of CGA on TAM-associated reproductive toxicity is absent in the literature. We, therefore, experimented on CGA's effect and TAM-mediated reproductive toxicity in rats. Cohorts of rats were treated with TAM (50 mg/kg) or co-treated with CGA (25 or 50 mg/kg) for 14 consecutive days. The result showed that treatment of CGA significantly increases testosterone, LH, and FSH levels compared to the TAM group. However, prolactin level was markedly decreased after pretreatment of CGA in TAM-treated rats. CGA abated TAM-induced decreases acid phosphatase, alkaline phosphatase, and antioxidant enzymes in the testis. CGA alleviated TAM-facilitated surges of reactive oxygen and nitrogen species, myeloperoxidase, nitric oxide, interleukin-1β, and tumor necrosis factor-alpha in rats epididymis and testes. Additionally, CGA increased anti-inflammatory cytokine -interleukin-10-, suppressed caspase-3 activity, and reduced pathological lesions in the examined organs of rats co-treated with CGA and TAM. CGA phytoprotective effect improved reproductive function occasioned by TAM-mediated toxicities in rats, by abating oxido-inflammatory damages and downregulating apoptotic responses. PRACTICAL APPLICATIONS: CGA protects against the damaging oxido-inflammatory responses incumbent on TAM metabolism. As an antioxidant abundant in plant-derived foods, CGA reportedly protects against inflammatory damage, hypertension, and neurodegenerative diseases. We present evidence that CGA ameliorates TAM-induced reproductive dysfunction by suppressing oxidative and inflammation stress downregulate apoptosis and improve reproductive function biomarker in rats.

Aflatoxin B1 (AFB1) is reported to elicit adverse reproductive outcomes in animals. Gallic acid (GA) is known to exhibit antioxidant and inflammatory bioactivities. The impact of GA on AFB1-facilitated reproductive dysfunction is nonexistent in literature. This investigation elucidated GA protective effect on AFB1-induced reproductive toxicities in rats, exposed for 28 consecutive days to AFB1 (75 µg/kg), or co-treated with GA (20 or 40 mg/kg) body weight. AFB1 significantly (p < 0.05) reduced testicular function biomarkers, serum hormonal levels, and functional sperm characteristics in experimental animals. GA abated AFB1-induced increases (p < 0.05) in lipid peroxidation and reactive oxygen and nitrogen species, suppressed myeloperoxidase, interleukin-1β, nitric oxide, and tumor necrosis factor-α levels—inflammatory biomarkers—in testes, epididymis, and hypothalamus. Furthermore, GA improved antioxidant defenses and alleviated reduction in interleukin-10, caspase-3 activation, and histological variations in epididymis, testes, and hypothalamus of rats dosed with AFB1. Conclusively, GA enhanced reproductive function in AFB1-exposed rats by modulating inflammatory, oxidative stress, and apoptosis mediators.Impact statementInfertility resulting from reproductive deficiency can be stressful. Exposure to aflatoxin B1, a dietary mycotoxin prevalent in improperly stored grains, is reported to elicit reproductive insufficiencies and infertility. We, therefore, examined the likely beneficial effect of gallic acid (GA) a phytochemical, recognized to exhibit in vitro and in vivo pharmacological bioactivities against oxidative stress and related inflammatory damages in rats, since AFB1 toxicities are predicated on oxidative epoxide formation, in a bid to proffer new evidence to advance the field of nutriceutical application from plant-derived chemopreventive agents. Our findings will advance the field of chemoprevention by presenting data absent in the literature on GA. Our results demonstrate further evidence for GA conferred protection against AFB1-mediated histological lesions in testes, epididymis, and hypothalamus of treated rats; suppresses oxidative damages, relieved inflammatory and apoptotic responses, restored sperm functional characteristics, and hormonal levels relevant for reproductive integrity and function.

The adverse effect of diclofenac administration on the male reproductive organ in both humans and rats has been reported. Selenium, a trace element vital in nutrition, plays a significant part in cellular redox homeostasis, including male reproduction. However, the impact of selenium on male reproductive toxicity associated with diclofenac administration is lacking in the literature. The current investigation assessed the modulatory effects of selenium on diclofenac-mediated reproductive toxicity in rats. Rats were treated for fourteen consecutive days, either with diclofenac (10 mg/kg) or co-treated with selenium (0.125 and 0.25 mg/kg) body weight. Sperm parameters, enzymes of testicular function, luteinizing, follicle-stimulating hormone and testosterone were assessed in addition to oxidative stress indices and histopathological changes. Selenium significantly alleviated diclofenac-induced decreases in sperm count and motility, testicular function enzymes and levels of luteinizing hormone and testosterone in serum. Moreover, selenium co-administration at 0.125 and 0.25 mg/kg inhibited the diclofenac-induced decrease of antioxidant enzyme activities and increased oxidative stress parameters-lipid peroxidation, reactive nitrogen and oxygen species-in epididymis and testes of rats. Selenium (0.25 mg/kg) alone ameliorated diclofenac-mediated histological injuries in exposed rats. Collectively, selenium enhanced testicular and epididymal function in diclofenac-treated rats by suppressing nitrosative and oxidative stress in rats.

The adverse effect of Aflatoxin B1 (AFB1 ) exposure in both humans and rodents has been widely reported. The beneficial health effects of gallic acid (GA) against AFB1 -induced toxicity in vitro have been published. Here, we present in vivo findings on AFB1 and GA on hepatorenal function in rats, exposed to AFB1 (75 µg/kg body weight) only or co-treated with GA (20 or 40 mg/kg) for 28 successive days. AFB1 significantly increased pro-inflammatory biomarkers and suppressed IL-10 levels in rats' liver and kidney. AFB1 caused increased (p < .05) oxidative stress by decreasing antioxidant enzymes levels and increasing levels of reactive oxygen and nitrogen species. Furthermore, reduction (p < .05) in cellular glutathione (GSH) levels and increased (p < .05) hepatorenal markers of toxicity were detected in rats treated with AFB1 . These observed alterations were, however, reversed in GA co-treated rats. GA ameliorated AFB1 -induced hepatorenal dysfunction by decreasing oxidative stress and inflammation in rats. PRACTICAL APPLICATIONS: GA can chemoprotect against the damaging effects of toxins contaminating food. GA is widely distributed in plants and in use in industries as antioxidant, immune-regulator, and natural defense agent against infections when consumed. Here, we disclosed that GA ameliorates AFB1 -induced hepatorenal dysfunction by suppressing oxidative stress, inflammation, and enhanced apoptosis, thus improving hepatorenal functions in rats exposed to AFB1.

The reproductive toxicity associated with furan exposure in both animals and humans has been documented. Protocatechuic acid (PCA), a dietary polyphenolic chemical, reportedly elicits beneficial effects on the male reproductive system. However, the influence of PCA on the reproductive toxicity related to furan exposure is unavailable in the literature. The current study evaluated the effects of PCA on the dysfunctional reproductive axis caused by furan exposure in rats. Experimental animals were exposed to furan (8 mg/kg) or co-treated with furan (8 mg/kg) and PCA (25 or 50 mg/kg) for twenty-eight successive days. Results revealed that PCA treatment significantly alleviated furan-mediated declines in sperm production and characteristic qualities as well as in serum levels of prolactin, luteinizing hormone, follicle-stimulating hormone, and testosterone. Further, PCA attenuated furan-induced reduction in antioxidant enzyme activities and testicular function marker enzymes, namely lactate dehydrogenase, glucose-6-phosphate dehydrogenase, acid phosphatase, and alkaline phosphatase. PCA effectively mitigated furan-mediated increases in myeloperoxidase activity, levels of reactive oxygen and nitrogen species, nitric oxide, tumour necrosis factor-alpha, and interleukin-1β in testes, epididymis, and hypothalamus of rats. Moreover, PCA increased anti-inflammatory cytokine interleukin-10 but suppressed caspase-9 and caspase-3 activities and ameliorated injuries in the testes, epididymis, and hypothalamus of furan-treated rats. In conclusion, PCA ameliorated deficits in the hypothalamic-pituitary-gonadal axis function in furan-exposed rats by suppressing oxido-inflammatory stress and apoptosis.

Evidence abounds—epidemiological and experimental—linking overexposure to manganese with hepatic and renal dysfunction. We investigated the beneficial effects of gallic acid or omega-3 fatty acids (ω-3-FA) on hepatorenal function in rats exposed to manganese (Mn). Rats were exposed to manganese (15 mg/kg) only or in the presence of ω-3-FA (30 mg/kg) or gallic acid (20 mg/kg) continuously for 14 days. Gallic acid or ω-3-FA co-treatment significantly ( P Impact statement Humans and animals are regularly exposed to toxic chemicals with subsequent adverse effects. Manganese exposure occurs via contaminated sources; over-exposure is associated with neuronal, hepatorenal dysfunction, etc. This work advances the field of natural chemopreventive agents by reporting evidence lacking in the literature on GA and ω-3-FA obtained primarily from the diet in protecting biological beings against toxic chemicals. Individually, GA and ω-3-FA exhibit various pharmacological effects. Our findings confirm the previous reports; however, we demonstrate the additional evidence for GA and ω-3-FA in abating toxic response incumbent on oxidative damage associated with manganese exposure. These findings further underscore the relevance of GA usage in food, cosmetics–pharmaceutical industries, and ω-3-FA as a safe supplement. Dietary supplements with GA and fish oil-rich in ω-3FA may be the potential natural therapy against hepatorenal injury in individuals inadvertently or occupationally exposed to manganese, thereby, promoting human and veterinary health outcomes.

Petroleum products-petrol, kerosene, and diesel-composed of volatile organic constituents contribute to air pollution. Exposure of gas station attendants (GSAs) to petroleum products fumes (PPFs) may account for occupation-related predisposition to respiratory toxicity and disease pathogenesis. We simulated GSA exposure to PPF inhalation and examined their effect on oxido-inflammatory responses, toxicity, and histopathological alterations in rat lungs, following 8-hours daily exposure for 60 and 90 days. Reactive oxygen and nitrogen species (RONS), oxidative stress and inflammatory biomarkers, namely: superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), TNF-α, IL-1β, xanthine oxidase (XO), nitric oxide (NO) activity were evaluated. Besides, histopathological examination of the lungs and trachea of exposed rats, PPF exposure resulted in significant (P < .05) increases in RONS, biomarkers of oxidative stress, pro-inflammation cytokines, and reduced (P < .05) GSH levels in rats, secondary to histopathological alteration in lungs and trachea cytoarchitecture examined in an exposure-duration-dependent manner. We conclude, therefore, that the observed biochemical and histological changes create a microenvironment that is permissive to diseases pathogenesis of the respiratory system via oxido-inflammatory mechanistic pathways.

The efficacy of methotrexate (MTX) as an anticancer drug is limited by some adverse effects including hepatic and renal toxicities. The present study investigated the possible protective effect of protocatechuic acid (PCA), a phenolic phytochemical widely present in several edible vegetables and fruits, on hepatorenal toxicity associated with MTX treatment in rats. Male Wistar rats were randomly assigned to five groups ( n = 10), namely control, MTX alone (20 mg/kg), PCA alone (50 mg/kg), and rats that were coadministered MTX and PCA at 25 and 50 mg/kg. The MTX was administered as a single intraperitoneal dose on the first day, whereas PCA treatment lasted 7 days. Results indicated that PCA significantly ( p < 0.05) abrogated MTX-mediated elevation in indices of hepatorenal toxicity. Furthermore, PCA protected against MTX-induced decreases in glutathione level and antioxidant enzyme activities as well as the increase in reactive oxygen and nitrogen species and lipid peroxidation in the liver and kidney of the treated rats. Administration of PCA markedly abated MTX-induced increases in interleukin-1β, tumor necrosis factor alpha, and caspase 3 activity in the rats. The biochemical data on the hepatorenal protective effects of PCA were well supported by the histological data. Collectively, PCA protected against MTX-induced hepatorenal toxicity via antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

The adverse health consequences of environmental, occupational, and dietary exposure to either diethylnitrosamine (DEN) or cadmium (Cd) have been widely investigated. However, because most environmental exposures to xenobiotics do not occur in isolation but in mixtures, the effects of simultaneous exposure to both DEN and Cd on hepatorenal function deserves investigation. The present study investigated the impact of 7 days oral co-exposure to 10 mg/kg body weight (b.w.) of DEN and 5 mg/kg b.w. of Cd on biomarkers of hepatic and renal functions, antioxidant defense systems, and oxidative stress indices in the liver and kidney of prepubertal rats. The results showed that the significant ( p < 0.05) increases in the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, urea, and creatinine following separate administration of DEN and Cd to rats were further increased in the co-exposure group. Moreover, marked decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase as well as glutathione levels following individual administration of DEN and Cd to rats were exacerbated in the co-exposure group. Further, the marked increase in the lipid peroxidation level and the histopathological lesions in the liver and kidney of rats treated with DEN or Cd alone were intensified in the co-exposure group These findings indicate that co-exposure to DEN and Cd elicited more severe hepatic and renal oxidative damage in the rats, thus suggesting a greater risk to humans who are co-exposed to them.

Exposure to the fungicide carbendazim (CBZ) has been associated with hepatorenal dysfunction. Quercetin, a naturally occurring polyphenolic phytochemical, reportedly possesses beneficial health effects. However, there is paucity of scientific information on the impact of quercetin on CBZ-induced hepatorenal damage. The present study investigated the protective mechanism of quercetin in CBZ-induced hepatic and renal damage in rats. The treatment groups consisted of control, CBZ alone (50 mg/kg), quercetin alone (20 mg/kg), and rats co-treated with CBZ and quercetin for 14 consecutive days. Quercetin co-treatment significantly ( p < 0.05) abated CBZ-induced increase in biomarkers of hepatorenal damage when compared to CBZ alone. Also, quercetin abrogated CBZ-mediated decrease in antioxidant status as well as the increase in reactive oxygen and nitrogen species and lipid peroxidation in the treated rats. Furthermore, quercetin significantly suppressed CBZ-mediated increase in interleukin-1β, tumor necrosis factor alpha, and caspase-3 activity in the liver and kidney of the rats. Histopathological examination demonstrated that the severity of CBZ-induced hepatic and renal injury was ameliorated in rats co-treated with quercetin. Taken together, quercetin-mediated hepatorenal protection in CBZ-treated rats involves antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

The present study investigated the impact of coexposure to fluoride and diethylnitrosamine (DEN) on hepatorenal function in adult rats. The animals were exposed to fluoride (15 mg/L in drinking water) and DEN (10 mg/kg) singly or coexposed to both compounds for 14 days. Results demonstrated that the fluoride or DEN mediated increase in hepatorenal toxicity was intensified in the coexposure group. Additionally, the decrease in antioxidant enzyme activities as well as the elevation in reactive oxygen and nitrogen species, and lipid peroxidation was markedly aggravated in rats coexposed to DEN and fluoride. Furthermore, the increase in levels of nitric oxide, tumor necrosis factor-α and interleukin-1β, myeloperoxidase and caspase-3 activities as well as histological lesions was more pronounced in the liver and kidney of rats coexposed to DEN and fluoride. Conclusively, coexposure to fluoride and DEN exacerbated hepatorenal damage via enhancement of oxido-inflammatory responses and caspase-3 activation in rats.

We examined the effect of protocatechuic acid (PCA) on methotrexate (MTX)-induced testicular and epididymal toxicity in Wistar rats, treated with MTX (20 mg/kg) alone or in combination with PCA (25 and 50 mg/kg) body weight for a week. PCA significantly abated MTX-mediated increase in reactive oxygen and nitrogen species generation and lipid peroxidation as well as enhances glutathione balance and antioxidant enzymes in the testes and epididymis of treated animals. PCA suppressed MTX-mediated increases in interleukin-1β, tumour necrosis factor alpha and caspase-3 activity in treated animals. Additionally, PCA treatment mediated increases in luteinising and follicle-stimulating hormones, prolactin and testosterone levels with marker enzymes of testicular function, accompanied with increase in sperm functionality in treated animals. Conclusively, PCA may serve as potential supplementation, enhancing reproductive health in males undergoing MTX therapy.

The present study investigated the individual and combined impact of organophosphorus pesticide chlorpyrifos (CPF) and manganese (Mn), a naturally occurring trace metal, on hepatorenal function in adult rats. The four experimental groups namely control, CPF alone (5 mg/kg), Mn alone (10 mg/kg) and the co-exposure group consisted of eight rats which were orally gavage for 14 consecutive days. Following sacrifice, the biomarkers of hepatorenal damage, antioxidant enzyme activities, myeloperoxidase (MPO) activity as well as levels of nitric oxide, reactive oxygen and nitrogen (RONS) species and lipid peroxidation (LPO) were analysed spectrophotometrically. Further, the concentration of tumour necrosis factor alpha (TNF-α), interleukin-1 β (IL-1β) and caspase-3 activity were assessed using ELISA. Results showed that the CPF-induced increase in biomarkers of hepatorenal toxicity were significantly (p

Clinical and experimental studies demonstrated that reproductive dysfunction is a non-lethal complication of diabetes. Protocatechuic acid (PCA) reportedly elicited several pharmacological effects in diabetic animals. However, there is paucity of information on the role of PCA in reproductive dysfunction associated with diabetes. The present study investigated the influence of PCA on the functional changes along the hypothalamic-pituitary-testicular axis in male diabetic rats. Streptozotocin (STZ)-induced diabetic rats were orally treated with PCA at 25 and 50 mg/kg body weight for 45 consecutive days. Results showed that PCA treatment significantly dwindled blood glucose level as well as prevented diabetes mediated decrease in body weight gain and organo-somatic indices of the testes and epididymis in the treated rats. Moreover, PCA increased the reproductive hormone levels, marker enzymes of testicular function and sperm functional characteristics in the treated rats. Further, PCA augmented the antioxidant status, inhibited lipid peroxidation and suppressed pro-inflammatory biomarkers including myeloperoxidase (MPO) activity, nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) levels as well as caspase-3 activity inhypothalamus, testes and epididymis of diabetic rats. Collectively, PCA effectively abrogated reproductive deficits in diabetic rats via mechanisms involving suppression of oxidative stress, inflammation and caspase-3 activity along with enhancement of sperm functional parameters. Thus, PCA may preserve reproductive health in humans suffering from diabetes.

Epidemiologic surveys and experimental data have revealed that environmental and dietary factors contribute to the etiology of colon cancer, which ranks third in cancer-related mortalities in the United States and fourth worldwide. In particular, human diet containing environmental carcinogens such as benzo(a)pyrene (B(a)P), a polycyclic aromatic hydrocarbon, has been the focus of investigators recently in relation to generated interest in looking at how it exerts its colorectal cancer. The present study investigated the effects of B(a)P on biomarkers of oxidative stress, inflammation and Wnt-signaling in colon of BALB/c mice following exposure to varying doses of 62.5, 125, and 250 mg/kg B(a)P for 7 days by oral gavage. Exposure to B(a)P induced marked oxidative stress accompanied by decrease in the colonic antioxidant enzyme activities and glutathione level with concomitant increase in myeloperoxidase activity, nitric oxide, and lipid peroxidation levels. Colon histopathology results showed B(a)P-related lesions characterized by atrophy, mucosal ulceration, and gland erosion in the mice. Immunohistochemistry analysis showed that B(a)P treatment increased the protein expression of nuclear factor kappa B, proinflammatory cytokines, namely tumor necrosis factor alpha and interleukin-1 β, as well as cyclooxygenase-2 and inducible nitric oxide synthase in the mice colon. Altered canonical Wnt signaling was confirmed by strong diaminobenzidine staining for p38 mitogen-activated protein kinase, b-catenin expression, and absence of adenomatous polyposis coli following B(a)P administration. Overall, our results show that exposure of mice to B(a)P induces colonic toxicity by mechanism involving oxidative and nitrosative stress, inflammation, and dsyregulation of Wnt/b-catenin signaling, and emphasizes the role of environmental polycyclic aromatic hydrocarbons like B(a)P in the pathology of colonic toxicity and tumorigenesis. Citation Format: Ebenezer O. Farombi, Babajide O. Ajayi, Isaac A. Adedara, Solomon E. Owumi. Induction of oxidative/nitrosative stress, proinflammatory cytokines and dysregulation of Wnt/beta-catenin signaling by benzo(a)pyrene in colons of BALB/c mice [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A40.

The anti-neoplastic use of Doxorubicin (DOX) is hampered by several limitations, including reproductive toxicity. Luteolin (LUT)–a phytochemical-biological benefits include antioxidative and anti-inflammatory actions. Here we examined the protective effect of LUT against DOX-induced reproductive toxicity in an in vivo model—male albino Wistar rats—randomly assigned to five groups and treated as follows: Control (corn oil 2 mL/kg; per os), LUT (100 mg/kg; per os), DOX (2 mg/kg) by intraperitoneal injections, co-treated groups received LUT (50 and 100 mg/kg) with DOX. Treatment with DOX alone, significantly (p > 0.05), reduced biomarkers of testicular function, reproductive hormone levels, testicular and epididymal antioxidant, and anti-inflammatory cytokine. DOX increased (p > 0.05) sperm morphological abnormalities, as well as reactive oxygen and nitrogen species, lipid peroxidation, xanthine oxidase, a pro-inflammatory cytokine, and apoptotic biomarkers. Furthermore, testicular and epididymal histological lesion complemented the observed biochemical changes in treated rats. LUT co-treatment resulted in a dosage-dependent improvement in rats’ survivability, antioxidants capacity, reduction in biomarkers of oxidative stress, pro-inflammatory cytokines, and apoptosis in rat’s testis and epididymis. Also, LUT treatment resulted in improved histological features in the testis and epididymis, relative to DOX alone treated rats. LUT co-treatment abated DOX-mediated reproductive organ injuries associated with pro-oxidative, inflammatory, and apoptotic mechanisms. LUT supplementation may serve as a phyto-protective agent in alleviating male reproductive organ toxic injuries associated with Doxorubicin therapy.

Environmental and occupational exposure to metal mixtures due to various geogenic and anthropogenic activities poses a health threat to exposed organisms. The outcome of systemic interactions of metals is a topical area of research because it may cause either synergistic or antagonistic effect. The present study investigated the impact of co-exposure to environmentally relevant concentrations of waterborne nickel (75 and 150 μg NiCl 2 L−1) and zinc (100 and 200 μg ZnCl2 L−1) mixtures on neurobehavioural performance of rats. Locomotor, motor and exploratory activities were evaluated using video-tracking software during trial in a novel arena and thereafter, biochemical and histological analyses were performed using the cerebrum, cerebellum and liver. Results indicated that zinc significantly (p

Certain industrial chemicals and food contaminants have been demonstrated to possess neurotoxic activity and have been suspected to cause brain-related disorders in humans. Acrylamide (ACR), a confirmed neurotoxicant, can be found in trace amount in commonly consumed human aliments as a result of food processing or cooking. This discovery aroused a great concern in the public, and increasing efforts are continuously geared towards the resolution of this serious threat. The broad chemical diversity of plants may offer the resources for novel antidotes against neurotoxicants. With the goal of attenuating neurotoxicity of ACR, several plants extracts or derivatives have been employed. This review presents the plants and their derivatives that have been shown most active against ACR-induced neurotoxicity, with a focus on their origin, pharmacological activity, and antidote effects. Copyright © 2015 John Wiley & Sons, Ltd.