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Cobalt is a ferromagnetic metal with extensive industrial and biological applications. To assess the toxic effects of, and mechanisms involved in cobalt chloride (CoCl2)-induced cardio-renal dysfunctions. Male Wistar rats were exposed orally, daily through drinking water to 0 ppm (control), 150 ppm, 300 ppm, and 600 ppm of CoCl2, respectively. Following exposure, results revealed significant (p < 0.05) rise in markers of oxidative stress, but decreased activities of catalase, glutathione peroxidase, glutathione-S-transferase, and reduced glutathione content in cardiac and renal tissues. There were significant increases in systolic, diastolic, and mean arterial blood pressure at the 300- and 600-ppm level of CoCl2-exposed rats relative to the control. Prolongation of QT and QTc intervals was observed in CoCl2 alone treated rats. Also, there were significant increases in the heart rates, and reduction in P wave, and PR duration of rats administered CoCl2. Histopathology of the kidney revealed peritubular and periglomerular inflammation, focal glomerular necrosis following CoCl2 exposure. Further, cyclooxygenase-2 and B-cell associated protein X expressions were upregulated in the cardiac and renal tissues of CoCl2-exposed rats relative to the control. Combining all, results from this study implicated oxidative stress, inflammation, and apoptosis as pathologic mechanisms in CoCl2-induced hypertension and cardiovascular complications of rats. [ABSTRACT FROM AUTHOR]

Sodium fluoride (NaF) is one of the neglected environmental toxicants that has continued to silently cause toxicity to both humans and animals. NaF is universally present in water, soil, and atmosphere. The persistent and alarming rate of increase in cardiovascular and renal diseases caused by chemicals such as NaF in mammalian tissues has led to the use of various drugs for the treatment of these diseases. The present study aimed at evaluating the renoprotective and antihypertensive effects of L-arginine against NaF-induced nephrotoxicity. Thirty male Wistar rats (150-180 g) were used in this study. The rats were randomly divided into five groups of six rats each as follows: Control, NaF (300 ppm), NaF + L-arginine (100 mg/kg), NaF + L-arginine (200 mg/kg), and NaF + lisinopril (10 mg/kg). Histopathological examination and immunohistochemistry of renal angiotensin-converting enzyme (ACE) and mineralocorticoid receptor (MCR) were performed. Markers of renal damage, oxidative stress, antioxidant defense system, and blood pressure parameters were determined. L-arginine and lisinopril significantly (P < 0.05) ameliorated the hypertensive effects of NaF. The systolic, diastolic, and mean arterial blood pressure of the treated groups were significantly (P < 0.05) reduced compared with the hypertensive group. This finding was concurrent with significantly increased serum bioavailability of nitric oxide in the hypertensive rats treated with L-arginine and lisinopril. Also, there was a significant reduction in the level of blood urea nitrogen and creatinine of hypertensive rats treated with L-arginine and lisinopril. There was a significant (P < 0.05) reduction in markers of oxidative stress such as malondialdehyde and protein carbonyl and concurrent increase in the levels of antioxidant enzymes in the kidney of hypertensive rats treated with L-arginine and lisinopril. The results of this study suggest that L-arginine and lisinopril normalized blood pressure, reduced oxidative stress, and the expression of renal ACE and mineralocorticoid receptor, and improved nitric oxide production. Thus, L-arginine holds promise as a potential therapy against hypertension and renal damage., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sodium fluoride (NaF) is one of the neglected environmental pollutants. It is ubiquitously found in the soil, water, and environment. Interestingly, fluoride has been extensively utilized for prevention of dental caries and tartar formation, and may be added to mouthwash, mouth rinse, and toothpastes. This study is aimed at mitigating fluoride-induced hypertension and nephrotoxicity with clofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist. For this study, forty male Wistar rats were used and randomly grouped into ten rats per group, control, sodium fluoride (NaF; 300 ppm) only, NaF plus clofibrate (250 mg/kg) and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. The administration of NaF was by drinking water ad libitum, while clofibrate and lisinopril were administered by oral gavage. Administration of NaF induced hypertension, and was accompanied with exaggerated oxidative stress; depletion of antioxidant defence system; reduced nitric oxide production; increased systolic, diastolic and mean arterial pressure; activation of angiotensin-converting enzyme activity and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); and testicular apoptosis. Treatment of rats with clofibrate reduced oxidative stress, improved antioxidant status, lowered high blood pressure through the inhibition of angiotensin-converting enzyme activity, mineralocorticoid receptor over-activation, and abrogated testicular apoptosis. Taken together, clofibrate could offer exceptional therapeutic benefit in mitigating toxicity associated with sodium fluoride., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cardiometabolic syndrome has been linked with dietary modification. Therefore, we investigated the effects of D-ribose-L-cysteine (DRLC) in rats fed with high fructose high fat (HFHF) diet. Twenty rats (n = 5), divided into 4 groups were concurrently exposed to HFHF and/or DRLC (250 mg/kg, p.o) during the 8 weeks study. The result showed that compared to control group, HFHF group had significant impairment in lipid and glucose homeostasis, increased cardiac xanthine oxidase, systolic blood pressure, heart rate, %body weight change and fluid intake. Also, there were significant reductions in HDL-C, cardiac (GPX, NO&GGT), feed intake and relative heart weight in the latter, relative to the former. However, there were no significant differences in most of the observed physical and biochemical changes in HFHF + DRLC group compared to control. DRLC alone did not disrupt the level of biomarkers. Conclusively, DRLC prevented the manifestation of oxidative stress and cardiometabolic syndrome in HFHF-diet fed rats., (Copyright © 2021. Published by Elsevier Masson SAS.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). This virus has become a global pandemic with unprecedented mortality and morbidity along with attendant financial and economic crises. Furthermore, COVID-19 can easily be transmitted regardless of religion, race, sex, or status. Globally, high hospitalization rates of COVID-19 patients have been reported, and billions of dollars have been spent to contain the pandemic. Angiotensin-converting enzyme (ACE) 2 is a receptor of SARS-CoV-2, which has a significant role in the entry of the virus into the host cell. ACE2 is highly expressed in the type II alveolar cells of the lungs, upper esophagus, stratified epithelial cells, and other tissues in the body. The diminished expressions of ACE2 have been associated with hypertension, arteriosclerosis, heart failure, chronic kidney disease, and immune system dysregulation. Overall, the potential drug candidates that could serve as ACE2 activators or enhance the expression of ACE2 in a disease state, such as COVID-19, hold considerable promise in mitigating the COVID-19 pandemic. This study reviews the therapeutic potential and pharmacological benefits of the novel ACE2 in the management of COVID-19 using search engines, such as Google, Scopus, PubMed, and PubMed Central., (Copyright: © Oyagbemi, et al.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the Coronavirus Disease 2019 (COVID-19). The COVID-19 pandemic has created unimaginable and unprecedented global health crisis. Since the outbreak of COVID-19, millions of dollars have been spent, hospitalization overstretched with increasing morbidity and mortality. All these have resulted in unprecedented global economic catastrophe. Several drugs and vaccines are currently being evaluated, tested, and administered in the frantic efforts to stem the dire consequences of COVID-19 with varying degrees of successes. Zinc possesses potential health benefits against COVID-19 pandemic by improving immune response, minimizing infection and inflammation, preventing lung injury, inhibiting viral replication through the interference of the viral genome transcription, protein translation, attachment, and host infectivity. However, this review focuses on the various mechanisms of action of zinc and its supplementation as adjuvant for vaccines an effective therapeutic regimen in the management of the ravaging COVID-19 pandemic. PRACTICAL APPLICATIONS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for the Coronavirus Disease 2019 (COVID-19), has brought unprecedented untold hardship to both developing and developed countries. The global race for vaccine development against COVID-19 continues with success in sight with attendant increasing hospitalization, morbidity, and mortality. Available drugs with anti-inflammatory actions have become alternative to stem the tide of COVID-19 with attendant global financial crises. However, Zinc is known to modulate several physiological functions including intracellular signaling, enzyme function, gustation, and olfaction, as well as reproductive, skeletal, neuronal, and cardiovascular systems. Hence, achieving a significant therapeutic approach against COVID-19 could imply the use of zinc as a supplement together with available drugs and vaccines waiting for emergency authorization to win the battle of COVID-19. Together, it becomes innovative and creative to supplement zinc with currently available drugs and vaccines., (© 2021 Wiley Periodicals LLC.)

Acute renal failure (ARF) has been documented as a life-threatening disease with high morbidity and mortality. We investigated the protective effect of Luteolin against ARF. In this study, forty-male Wistar albino rats were randomly divided into four groups ( n  = 10). Group A received normal saline. Group B received glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.). Groups C and D were pretreated with Luteolin 100 and 200 mg/kg for 7 days, and thereafter administered Glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.). Administration of glycerol significantly increased systolic blood pressure, diastolic blood pressure and mean arterial pressure. Renal protein carbonyl and xanthine oxidase increased significantly while significant reduction in the activity of renal glutathione peroxidase, glutathione S-transferase and glutathione reductase was observed in the glycerol intoxicated rats. Furthermore, administration of glycerol led to significant increases in serum creatinine and blood urea nitrogen together with reduction in nitric oxide (NO) bioavailability. Immunohistochemistry revealed that glycerol intoxication enhanced expressions of kidney injury molecule 1, nuclear factor kappa beta and cardiac troponin (CTnI). However, Luteolin pretreatment normalized blood pressure, reduced markers of oxidative stress, renal damage, and improved NO bioavailability. Luteolin also downregulated the expressions of kidney injury molecule 1, nuclear factor kappa beta and cardiac troponin. Together, Luteolin might open a novel therapeutic window for the treatment of acute renal failure and cardiac complication.

Hypertension is the most common cardiovascular disease that affects approximately 26% of adult population, worldwide. Rutin is one of the important flavonoids that is consumed in the daily diet, and found in many food items, vegetables, and beverages. Uninephrectomy (UNX) of the left kidney was performed, followed by induction of hypertension. The rats were randomly divided into four groups of 10 rats: group 1-Sham-operated rats; group 2-UNX rats, group 3-UNX-L-NAME (40 mg/kg) plus rutin (100 mg/kg bwt), and groups 4-UNX-L-NAME plus lisinopril (10 mg/kg bwt), orally for 3 weeks. Results revealed significant heightening of arterial pressure and oxidative stress indices, while hypertensive rats treated with rutin had lower expressions of angiotensin converting enzyme (ACE) and mineralocorticoid receptor in uninephrectomized rats. Together, rutin as a novel antihypertensive flavonoid could provide an unimaginable benefits for the management of hypertension through inhibition of angiotensin converting enzyme and mineralocorticoid receptor. PRACTICAL APPLICATIONS: Hypertension has been reported to be the most common cardiovascular disease, affecting approximately 26% of the adult population worldwide with predicted prevalence to increase by 60% by 2025. Recent advances in phytomedicine have shown flavonoids to be very helpful in the treatment of many diseases. Flavonoids have been used in the treatment and management of cardiovascular diseases, obesity and hypertension. The study revealed that rutin, a known flavonoid inhibited angiotensin converting enzyme (ACE), angiotensin 2 type 1 receptor (ATR1), and mineralocorticoid receptor (MCR), comparable to the classic ACE inhibitor, Lisinopril, indicating the novel antihypertensive property of rutin. Therefore, flavonoids such as rutin found in fruits and vegetables could, therefore, serve as an antihypertensive drug regimen. Combining all, functional foods rich in flavonoids could be used as potential therapeutic candidates for managing uninephrectomized hypertensive patients., (© 2020 Wiley Periodicals LLC.)

Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. In this study we investigated the antihyperuricemic and nephroprotective potential of RA-3, a plant-derived lanosteryl triterpene. The antihyperuricemic and nephroprotective effect of RA-3 was investigated using the adenine and gentamicin induced hyperuricemic and nephrotoxicity rat model. Following the induction of hyperuricemia and nephrotoxicity, the experimental model rats (Sprague Dawley) were orally administered with RA-3 at 50 and 100 mg/kg body weight, respectively, daily for 14 days. Treatment of the experimental rats with RA-3, especially at 100 mg/kg, effectively lowered the serum renal dysfunction (blood urea nitrogen and creatinine) and hyperuricemic (uric acid and xanthine oxidase) biomarkers. These were accompanied by increased antioxidant status with decrease in malondialdehyde content. A much improved histomorphological structure of the kidney tissues was also observed in the triterpene treated groups when compared to the model control group. It is evident that RA-3 possesses the antihyperuricemic and nephroprotective properties, which could be vital for prevention and amelioration of kidney disease.

Hypertension is a condition with chronic elevation of blood pressure and a common preventable risk factor for cardiovascular disease with attendant global morbidity and mortality. The present study investigated the novel antihypertensive and neuroprotective effect of Naringenin on L-N G -Nitro arginine methyl ester (L-NAME) induced hypertension together with possible molecular mechanism of action. Rats were divided into four groups. Rats in Group A were normotensive. The hypertensive group (Group B) received 40 mg/kg) of L-NAME alone while Groups C and D were concurrently administered Naringenin (50 mg/kg) or Lisinopril (10 mg/Kg) together with L-NAME orally for 3 weeks. Blood pressure parameters, markers of oxidative stress and renal damage were measured. The immunohistochemistry of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme were also determined. Results indicated significant increases in malondialdehyde, advanced oxidation protein products, protein carbonyl contents and decrease in serum nitric oxide bioavailability in hypertensive rats. Furthermore, there were significant increases in serum myeloperoxidase, urinary creatinine, albumin and blood urea nitrogen in hypertensive rats in comparison to hypertensive rats treated with either Naringenin or Lisinopril. Immunohistochemistry reveal significant expressions of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme in hypertensive rats. However, co-treatment with either Naringenin or Lisinopril mitigated both renal and neuronal oxidative stress, normalized blood pressure and lowered the expressions of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme. Collectively, Naringenin offered a novel antihypertensive and neuroprotective effect through down regulation of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Fluoride is an environmental contaminant that is ubiquitously present in air, water, and soil. It is commonly added in minute quantity to drinking water, toothpaste, and mouth rinses to prevent tooth decay. Epidemiological findings have demonstrated that exposure to fluoride induced neurodevelopmental toxicity, developmental neurotoxicity, and motor disorders. The neuroprotective effect of clofibrate, a peroxisome proliferator-activated receptor alpha agonist, was investigated in the present study. Forty male Wistar rats were used for this study and randomly grouped into 10 rats per group as control, sodium fluoride (NaF) alone (300 ppm), NaF plus clofibrate (250 mg/kg), and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. NaF was administered in drinking water while clofibrate and lisinopril were administered by oral gavage. Markers of neuronal inflammation and oxidative stress, acetylcholinesterase activity, and neurobehavioral (hanging wire and open field) tests were performed. Immunohistochemistry was performed on brain tissues, and they were probed with glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, and cerebellar Ca 2+ -binding protein calbindin-D28k. The results showed that NaF significantly increased of oxidative stress and neuroinflammation and inhibited AChE activity. Immunostaining showed reactive astrocytes, microgliosis, loss of dendritic spines, and arborization in Purkinje cells in rats administered only NaF. Neurobehavioral results showed that cotreatment of NaF with clofibrate improved muscular strength and locomotion, reduced anxiety, and significantly reduced astrocytic count. Overall, cotreatment of NaF with either clofibrate or lisinopril showed neuroprotective effects by mitigating neuronal inflammation and oxidative and motor incoordination. Hence, clofibrate could be seen as a novel drug candidate against neurodegeneration and motor disorders., (© 2019 Wiley Periodicals, Inc.)

Aims: Hypertension is a global disease that has been combating the world health for ages. Peristrophe roxburghiana (PR) is used in traditional medicine to treat hypertension and other ailments. The present study examined phytochemical constituents, antioxidant activities and GC-MS analysis of extracts of PR leaf and also evaluated their anti-hypertensive and anti-lipidemic effects in NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats., Methods: Wistar rats were grouped into two groups: control and hypertensive. Hypertension was induced in the hypertensive group by oral gavage of 60 mg/kg b.w of L-NAME for 3 weeks. After induction, the hypertensive group was randomly sub-grouped into hypertensive, hypertensive treated and hypertensive untreated groups. These were orally gavaged respectively with 60 mg/kg b.w of L-NAME, 60 mg/kg b.w/day of L-NAME +200 mg/kg b.w of different extracts of PR (aqueous, ethanolic and methanolic extracts) and 60 mg/kg b.w of L-NAME +20 mg/kg b.w ramipril for 3 weeks. The blood pressure was measured by tail-cuff method at the third and sixth weeks., Key Findings: The results showed that the extracts of PR significantly decrease blood pressure, pro-atherogenic lipids and atherogenic ratios in L-NAME hypertensive rats. White blood cells count, neutrophil count and creatinine level were also effectively decreased by the extracts. Furthermore, the extracts increase serum nitric oxide (NO) level, anti-atherogenic lipid, glutathione level, lymphocyte and platelet count in the rats., Significance: Extracts of PR leaf decrease blood pressure and increase NO level in L-NAME hypertensive rats and also corrected the hyperlipidemia and inflammatory response arising from the reduction in NO bioavailability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Azadirachta indica (AI) is a medicinal plant with reported antioxidant and cardio-protective properties. The use of plant-based polyphenols has become greatly increased in the last one decade. The present study investigated the protective effect of the polyphenol-rich fraction (PRF) of the methanol-extract of Azadirachta indica against N ω -Nitro-L-Arginine Methyl Ester (L-NAME) induced hypertension and cardiorenal dysfunction in rats. Fifty (50) Wistar albino rats were grouped into five groups. Group A, the control, was administered potable water. Groups B-E received orally, 40 mg/kg of L-NAME only, 40 mg/kg of L-NAME and 100 mg/kg of AI extract, 40 mg/kg of L-NAME and 200 mg/kg of AI extract, and 40 mg/kg of L-NAME and 25 mg/kg of captopril, respectively for 21 days. The results of the present study revealed that L-NAME administration led to a significant increase in systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. Markers of oxidative stress (malondialdehyde,protein carbonyl) increased significantly while there was reduction in reduced glutathione level, activities of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase as well nitric oxide bioavailability. Immunohistochemistry revealed higher expressions of nuclear factor kappa beta (NF- k B) and kidney injury molecule 1(Kim-1) and lower expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) in hypertensive rats. Our results indicated that with PRF of AI restored high blood pressure, reduced markers of oxidative stress, normalized serum NO bioavailability and increased the expressions of Nrf2. Hence, PRF of Azadirachta indica could be used for the treatment of hypertension., Competing Interests: The authors have declared no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Sodium fluoride is one of the neglected environmental contaminants. Inorganic fluorides in the environment are found in the air, water, and land. In the study, forty-male Wistar albino rats were randomly divided into four groups with 10 rats in a group. Group A was the control group which was given normal saline, Group B was exposed to 300 ppm of NaF in drinking water, while Groups C and D received NaF along Rutin (100 mg/kg and 200 mg/kg) orally daily for a week. Administration of NaF alone led to significant increases in blood pressure, and deceased serum nitric oxide. Immunohistochemistry revealed higher expressions of kidney injury molecule I (Kim-1), nuclear factor kappa beta (NF-κB), and down regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in rats administered NaF. Rutin co-treatment with NaF normalized blood pressure, lowered Kim-1 and NF-κB expressions, and improved nitric oxide bioavailability., (© 2018 Wiley Periodicals, Inc.)

The use of sodium fluoride (NaF) as a major ingredient for tooth paste, mouth wash, and mouth rinse has become inevitable in our day-to-day life. However, flavonoids such as Luteolin might be of great value in the prevention of toxicity associated with accidental or inevitable ingestion of NaF. In the study, 40 male Wistar albino rats were randomly divided into four groups with 10 rats in a group. Group A was the control group and received normal saline, Group B was exposed to NaF at 300 ppm (300 mg/L) in drinking water daily for a week, Groups C and D were exposed to 300 ppm (300 mg/L) of NaF and coadministered with Luteolin orally daily at a dosage of 100 mg/kg and 200 mg/kg for the same time point. Our results indicated that NaF caused significant increases in systolic blood pressure, diastolic blood pressure, mean arterial pressure, malondialdehyde, protein carbonyl, myeloperoxidase, advanced oxidative protein products, together with significant reductions in glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and nitric oxide (NO) bioavailability. The electrocardiogram results showed that NaF alone caused significant prolongation of QT and QTc intervals. Immunohistochemistry revealed that NaF caused increase expressions of Kidney injury marker 1 (Kim-1), nuclear factor kappa bet (NF-κB), nuclear factor erythroid 2-related factors 2 (Nrf2), and cardiac troponin I (CTnI). Together, Luteolin coadministration with NaF improved NO bioavailability, reduced high blood pressure, markers of oxidative stress, reversed prolongation of QT and QTc intervals, and lowered the expressions of Kim-1, NF-κB, and CTnI. © 2018 BioFactors, 44(6):518-531, 2018., (© 2018 International Union of Biochemistry and Molecular Biology.)

Hypertension is one of the silent killers in the world with high mortality and morbidity. The exposure of humans and animals to fluoride and/or fluoride containing compounds is almost inevitable. This study investigated the modulatory effects of quercetin on sodium fluoride (NaF)-induced hypertension and cardiovascular complications. Forty male rats were randomly separated into four groups (n =10). Group A animals served as the control, rats in Group B were exposed to 300 ppm of NaF, Groups C and D animals were exposed to 300 ppm of NaF along with quercetin orally at 50 mg/kg and 100 mg/kg orally by gavage, while NaF was administered in drinking water, respectively, for a week. Administration of NaF caused severe hypertension as indicated with significant increases in the systolic, diastolic, and mean arterial blood pressure, together with prolonged ventricular depolarization (QRS) and the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT) intervals when compared with controls. NaF significantly decreased the activities of antioxidant enzymes, caused increase in markers of oxidative stress and renal damage when compared with controls. Immunohistochemical staining revealed lower expressions of Hsp70, ERK, and PPARγ in the heart, kidney, and aorta of rats-administered NaF relative to the controls. Together, quercetin co-treatment with NaF restored blood pressure, normalized QRS interval, and improved antioxidant defense system. © 2018 BioFactors, 44(5):465-479, 2018., (© 2018 International Union of Biochemistry and Molecular Biology.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Sodium arsenite (NaAsO 2 ) is one of the major environmental toxicants with severe toxicological consequences in some developing and developed countries. Rats in Group A received normal saline. Genotoxicity and apoptosis were induced by single intraperitoneal injection of 10 mg/kg sodium arsenite to rats in Groups B-F. Rats in Groups C and D had earlier been pretreated with Azadirachta indica (100 and 200 mg/kg) or E and F with vitamin E (50 and 100 mg/kg), respectively. Markers of oxidative stress, inflammation, hepatic damage, genotoxicity, and apoptosis were assessed. Pretreatment of rats with either Azadirachta indica or vitamin E led to a significant (p <.05) increase in the activities of glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) in the liver compared to the group that received NaAsO 2 alone. Markers of oxidative stress and inflammation, malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ) generation, nitric oxide (NO), and myeloperoxidase (MPO), were significantly (p <.05) lowered in rats pretreated with Azadirachta indica or vitamin E. The frequency of micronucleated polychromatic erythrocytes (MNPCEs) and expression of caspase-3 were significantly (p <.05) reduced in rats pretreated with either Azadirachta indica or vitamin E compared to rats intoxicated with arsenite. Histopathology of the liver showed areas of infiltration of inflammatory cells with deaths of numerous hepatocytes in NaAsO 2 -intoxicated rats, and these were reversed by Azadirachta indica. Together, we report for the first time the genoprotective and antiapoptotic effect of Azadirachta indica by a significant reduction in the frequency of micronuclei-induced apoptosis and oxidative stress by arsenic intoxication.

Nitric oxide (NO) is major endothelial relaxing factor and reduction in its bioavailabilty has been linked to hypertension. Furthermore, high lipid content is a strong risk factor predisposing to cardiovascular diseases. The principal focus of this study was to investigate the effect of blockade of nitric oxide synthase (NOS) on serum lipid content in rats. Male Wistar rats (150-170 g, n = 15) were randomly divided into two groups designated control (n = 5), and L-Name group (n = 10) and were gavage with distilled water and 60 mg/kg of L-NAME respectively daily for three weeks. After 3 weeks, the L-NAME group was sub-divided into two sub-groups (n = 5 each): L-NAME (60 mg/kg of L-NAME), and L-NAME plus ramipril (LR) (60 mg/kg of L-NAME plus 20 mg/kg of ramipril) and were treated daily for another three weeks. The blood pressure (BP) of the conscious rats was measured by tail-cuff method at the onset, at the third and at the sixth weeks of the experiment; while serum lipid contents and NO were measured at the third and sixth weeks. At the end of the experiment blood sample was drawn by ocular puncture for evaluation of lipid profile and NO, and the animals were later euthanized by overdose of anaesthesia. Data were analyzed using ANOVA at p < 0.05. There was a significant increase in BP, triglyceride, total cholesterol, low density lipoprotein-cholesterol, and atherogenic indices in L-NAME group compared to the control and LR group (p < 0.05); NO and high density lipoprotein-cholesterol was significant lower in the L-NAME group compared to control and LR (p < 0.05). In conclusion, reduction in NO bioavailability alters lipid metabolism, which was rectified by ramipril., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Toxicities due to fluoride exposure from natural and industrial sources occur commonly in man and animals with severe consequences ranging from mild cardiac derangements to sudden death. In this study, we investigated the protective effects of the methanol extract of Azadirachta indica (AI) against sodium fluoride (NaF)-induced hypertension and genotoxicity in rats., Methods: Sixty rats were divided into six groups of ten rats each as follows: Group A, the control group received distilled water; Group B rats were administered NaF at 600 ppm in drinking water; Groups C and D rats were pre-treated with the methanol extract of AI and thereafter administered NaF at 600 ppm in drinking water for 7 consecutive days; Groups E and F rats were co-administered with AI and NaF., Results: The administration of NaF caused significant (p<0.05) increases in the blood pressure, markers of oxidative stress, serum myeloperoxidase, xanthine oxidase values in NaF-alone treated rats, compared with the control. Significant (p<0.05) decreases were observed in cardiac and renal antioxidant defence system in rats administered NaF alone compared with the control group. NaF treatment also resulted in a reduction in the expressions of extracellular signal-regulated kinase (ERK) 1/2 in cardiac and renal tissues of NaF-treated rats. Moreover, NaF treatment elicited an increase in the frequency of micronucleated polychromatic erythrocytes when compared with the control group., Conclusions: This study shows the protective effect of AI on NaF-induced hypertension and genotoxicity through antioxidant and ERK 1/2 signaling in rats.

Hepatotoxicity has been found to be one of the main side effects associated with doxorubicin (Dox) administration in cancer therapy. The aim of the present study was to examine the ameliorative effect of gallic acid (GA) in Dox-induced hepatotoxicity. Sixty male Wistar rats of 10 rats per group were used in this study and were randomly divided into 6 experimental groups (A-F). Rats in Group A served as the control group and received distilled water orally for 7 days; Group B was given Dox at 15 mg/kg body weight intraperitoneally (IP) on Day 8. Group C was given GA at 60 mg/kg body weight orally for 7 days + Dox at 15 mg/kg IP on Day 8. Group D was given GA at 120 mg/kg body weight orally for 7 days + Dox at 15 mg/kg IP on day 8. Rats in Groups E and F were administered GA alone at 60 and 120 mg/kg body weight orally for 7 days, respectively. Dox administration led to a significant reduction in hepatic reduced glutathione and nonprotein thiol (NPT) together with significant increase in hepatic malondialdehyde, hydrogen peroxide generation, superoxide dismutase, and catalase activity; hepatic glutathione peroxidase and glutathione-S-transferase activity were significantly inhibited in Dox-treated rats. The serum alanine aminotransferase (ALT), alkaline phosphatase, and total bilirubin concentrations were significantly elevated following Dox administration. Pretreatment with GA ameliorated Dox-induced hepatotoxicity and oxidative stress. The results suggest that GA may offer protection against hepatic damage in Dox cancer chemotherapy.

Background: The use of doxorubicin (DOX) as an antineoplastic agent has been greatly limited because of the myriad of toxic sequelae associated with it. The aim of this study was to assess the protective effects of gallic acid (GA) on DOX-induced cardiac toxicity in rats., Methods: Sixty male rats (Wistar strain) were used in this study. They were divided into six groups (A-F) each containing 10 animals. Group A was the control. Rats in Groups B, C, and D were treated with DOX at the dosage of 15 mg/kg body weight i.p. Prior to this treatment, rats in Groups C and D had been treated orally with GA for 7 days at the dosage of 60 and 120 mg/kg, respectively. Animals from Groups E and F received only 60 and 120 mg/kg GA, respectively, which were administered orally for 7 days., Results: The exposure of rats to DOX led to a significant (p<0.05) decrease in the cardiac antioxidant defence system and elevation of creatine kinase myocardial band and lactate dehydrogenase. The electrocardiography results showed a significant decrease in heart rate, QRS, and QT-segment prolongation. GA alone improved the antioxidant defence system., Conclusions: The GA pretreatment significantly alleviated GA-associated ECG abnormalities, restored the antioxidant status and prevented cardiac damage.

We investigated the effects of withdrawal from Sodium arsenite (NaAsO 2 ) on the hepatic and antioxidant defense system in male Wistar rats using a before and after toxicant design. Rats were orally gavaged daily with varying doses of NaAsO 2 for a period of 4 weeks. One half of the population was sacrificed and the remaining half had the toxicant withdrawn for another further 4 weeks. Biochemical and immunohistochemical techniques were used to assess the impact of withdrawal on the erythrocyte and hepatic systems. Exposure of Wistar rats to NaASO 2 led to a significant (p < 0.05) increase in hepatic and erythrocyte markers of oxidative stress (malondialdehyde, thiol contents and hydrogen peroxide generation). Concurrently, there was a significant (p < 0.05) increase in hepatic and erythrocyte antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and superoxide dismutase) following exposure. Withdrawal from NaAsO 2 exposure led to a decline in both erythrocyte and hepatic markers of oxidative stress and together with a significant improvement in antioxidant defense system. Histopathology and immunohistochemistry revealed varying degrees of recovery in hepatocyte ultrastructure alongside increased expression of the pro-survival protein Kinase B (Akt/PKB) after 4 weeks of NaAsO 2 withdrawal. Conclusively, withdrawal from exposure led to a partial recovery from oxidative stress-mediated hepatotoxicity and derangements in erythrocyte antioxidant system through Akt/PKB pathway.

Electrocardiographic and blood pressure measurements are extremely valuable diagnostic tools in the evaluationof the cardiovascular system of living animals. In this study, 6-lead electrocardiograms were recorded from five male captiveAfrican lions (Panthera leo). Also, blood pressure measurements were recorded and compared from three different sites;fore limb, hind limb and the tail, were recorded. Immobilization was done with a combination of Ketamine Hydrochloride(10mg/kg) and Xylazine (3mg/kg). Measurements were recorded as mean ± standard deviation. ECG readings were analysedusing descriptive statistics while blood pressure readings were compared using ANOVA at a 5% level of significance. Heartrate was 66±11.6 beats per minute. The heart rhythm was sinus in all the animals. Mean Electrical Axis (MEA) was between+810 and +930 degrees (Mean +89±5). Three animals had their MEA between +810 and +890 while two had MEA between+910 and +930. Fore limb measurements for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DAP) and MeanArterial Pressure (MAP) were 177.6±6.8 mmHg, 157.2±5.9 mmHg and 168.6±5.2 mmHg respectively. Hind limbmeasurements for the SBP, DBP and MAP were 135.4±9.5 mmHg, 120.6±5.9 mmHg and 123.0±6.8 mmHg respectivelywhile the tail measurements for the SBP, DBP and MAP were 149.6±8.3 mmHg, 132.8±5.9 mmHg and 137.2±5.8 mmHgrespectively. There was weak correlation between forelimb vs hindlimb and forelimb vs tail comparisons of SBP, DBP andMAP. However, a strong positive correlation was found between hindlimb and tail comparisons of those parameters. Resultsfrom this study should serve as a guide in the cardiovascular monitoring of captive African Lions immobilized with axylazine-ketamine combination.

Background: Azadirachta indica is widely distributed in Africa, Asia and other tropical parts of the world. A. indica (AI) is traditionally used for the treatment of several conditions including cancer, hypertension, heart diseases and skin disorders. Intestinal ischaemia-reperfusion is a common pathway for many diseases and may lead to multiple organ dysfunction syndrome and death., Objective: In this study, we investigated the ameliorative effects of AI on intestinal ischaemia-reperfusion injury-induced cardiorenal dysfunction., Materials and Methods: Sixty rats were divided into 6 groups; each containing 10. Corn oil was orally administered to group A (control) rats for 7 days without intestinal ischaemia-reperfusion injury. Group B underwent intestinal ischaemia-reperfusion injury (IIRI) without any pre-treatment. Groups C, D, E and F were pre-treated orally for 7 days with 100 mg/kg AI (100 and (200 mg/kg) vitamin C (100 and 200 mg/kg) respectively and thereafter underwent IIRI on the 8th day., Results: The cardiac and renal hydrogen peroxide increased significantly whereas serum xanthine oxidase and myeloperoxidase levels were significantly elevated (p < 0.05) in IIRI only when compared to the control. The cardiac and renal reduced glutathione, glutathione peroxidase, protein thiol, non-protein thiol and serum nitric oxide (NO) decreased (p < 0.05) significantly following IIRI. Immunohistochemical evaluation of cardiac and renal tissues showed reduced expressions of the extracellular signal regulated kinase (ERK1/2) in rats with IIRI only. However, pre-treatment with A. indica and vitamin C significantly reduced markers of oxidative stress and inflammation together with improvement in antioxidant status. Also, reduced serum NO level was normalised in rats pre-treated with A. indica and vitamin C with concomitant higher expressions of cardiac and renal ERK1/2., Conclusions: Together, A. indica and vitamin C prevented IRI-induced cardiorenal dysfunction via reduction in oxidative stress, improvement in antioxidant defence system and increase in the ERK1/2 expressions. Therefore, A. indica can be a useful chemopreventive agent in the prevention and treatment of conditions associated with intestinal ischaemia-reperfusion injury., (Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.)

Introduction: The medicinal properties of Azadirachta indica have been harnessed for many years in the treatment of many diseases in both humans and animals., Materials and Methods: Twenty-five apparently healthy dogs weighing between 3 and 8 kg were randomly divided into five groups with five dogs in each group. Ameliorative effect of A. indica on erythrocyte antioxidant status and markers of oxidative stress were assessed. Liver and kidney function tests were also performed., Results: Pre-treatment with methanolic extract of Azadirachta indica (MEAI) at different doses did not significantly alter the values of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity in Trypanosoma brucei infection. Although, serum creatinine significantly (P < 0.05) decreased with pre-treatment with 50 mg/kg A. indica, after 2 weeks of T. brucei infection. However, the reduced glutathione (GSH) content of the erythrocyte increased significantly in animals pre-treated with 50 mg/kg and 200 mg/kg of A. indica respectively. Markers of oxidative stress such as malondialdehyde and hydrogen peroxide generated were higher in animals infected with T. brucei with no significant (P >0.05) difference compared to the values obtained in pre-treated animals. Pre-treatment with 100 mg/kg and 200 mg/kg of A. indica significantly (P < 0.05) decreased serum myeloperoxidase activity at 2 weeks post-infection with T. brucei., Conclusion: From this study, MEAI showed significant ability to attenuate oxidative stress and inflammation during experimental T. brucei infection.