Search

Liver cancer, specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related deaths, following pancreatic cancer. The 5-year overall survival rate for HCC remains relatively low. Currently, there are multiple treatment options available for HCC, including systemic drugs, minimally invasive local therapies such as radiofrequency ablation, transarterial chemoembolization (TACE), and arterial radioembolization (TARE), as well as surgical interventions like liver resection or transplantation. However, the effectiveness of drug delivery to the cancerous liver is hindered by pathophysiological changes in the organ. In order to address this challenge, lipid-based nanoparticles (LNPs) have emerged as promising platforms for delivering a diverse range of therapeutic drugs. LNPs offer various structural configurations that enhance their physical stability and enable them to accommodate different types of cargo with varying mechanical properties and degrees of hydrophobicity. In this article, we provide a comprehensive review of the current applications of LNPs in the development of anti-HCC therapies. By examining the existing research, we aim to shed light on the potential future directions and advancements in this field.

IntroductionThe therapeutic efficacy of oral administration of Ziziphus jujube in the context of uterine adhesion (UA) and its impact on pregnancy outcomes was investigated.MethodsIn a rat UA model, Z. jujube was evaluated for its ability to mitigate injury-induced uterine adhesion bands, uterine shortening, and enhance endometrial regeneration. The assessment included analysis of gland numbers, uterine endometrial thickness, and regulation of inflammatory cytokines. The antioxidant properties of Z. jujube were also studied through antioxidant enzyme activity in uterine tissue homogenates. Fibrotic changes were examined through histological Trichrome staining and analysis of pro-fibrotic factors.ResultsTreatment with Z. jujube resulted in a significant reduction in uterine tissue fibrosis, as evidenced by histological evaluation and reduced expression of fibrotic markers. The intervention demonstrated positive outcomes in embryonic development, pregnancy rates, and pregnancy outcomes. Z. jujube effectively inhibited the formation of extra-uterine adhesion bands to internal organs. No toxicity-related morphological changes were observed in vital organs of the Z. Jujube-treated group.DiscussionThe results collectively indicate that Z. jujube is a safe and potent natural product with anti-inflammatory and anti-fibrotic properties, highlighting its potential as a novel candidate for clinical studies targeting UA in patients.

Abstract Intrauterine adhesion (IUA), also referred to as Asherman’s syndrome, is characterized by fibrosis, inflammation, and can cause amenorrhea and infertility due to abnormal endometrial healing. Histological and Molecular methods were used to evaluate the efficacy of EPO, which is traditionally known for its anti-inflammatory and fibrinolytic properties, in preventing the formation of IUA. Oral administration of EPO reduced the formation of adhesion bands and promoted endometrial regeneration. EPO administration decreased extracellular matrix accumulation, evidenced by the down-regulation of tissue COL1A1 and COL3A1 expression. The anti-inflammatory effect of EPO was confirmed by a reduction in oxidants and down-regulation of pro-inflammatory cytokines including TNF-α, IL-6, IFN-γ, and IL-1β. Furthermore, EPO improved embryonic development parameters, including size and weight of embryo, as well as increased embryo count and live embryo percentage in the rat IUA model. EPO also positively enhanced implantation markers, particularly enlargement and mass gain in the placenta of the treated group, consequently improving pregnancy outcomes such as the number of babies, percent of live babies, baby weight and gestation time. Histopathological investigation provides evidence that oral administration of EPO showed no toxicity on the main three organs including liver, kidney and heart. These results showed that EPO can be considered as a safe and natural product with potent anti-inflammatory and fibrinolytic properties without any observed side effects for the treatment of IUA.

Objective: Muscle atrophy due to immobility is a common complication of many diseases and a consequence of therapeutic processes. Immobility and inactivity have been shown to be associated with increased inflammation. The aim of this study was to investigate the therapeutic potential of Wild Bitter Melon (WBM) (Momordica charantia Linn) on muscle atrophy due to immobility in a mouse model.Materials and Methods: This study was performed in two phases of atrophy and recovery on male BALB/c mice which were divided into 3 groups: control, immobilized, and experimental. The treatment period with WBM at a dose of 400 mg/kg daily by gavage was 17 days, including 7 days of being immobilized and 10 days of recovery. At the end of each phase, half of the mice from each group were examined regarding the four limb grip strength, and then histological and biochemical analyses were done.Results: The tissue level of malondialdehyde (MDA) oxidative stress index in the atrophy phase in the atrophy group (5.4567±0.522) nmol/g compared to the control group (3.455±0.065) nmol significantly (p 0.001)

Muscle atrophy due to limb immobilization and inactivity is a common consequence of many diseases and treatment processes. One of the systems activated in inflammatory conditions is the renin-angiotensin system (RAS). The present study was conducted with the aim of investigating the effects of one of the angiotensin-converting enzyme (ACE) inhibitors, enalapril, on improving muscle atrophy caused by immobility. The study was conducted in three groups: a control, an atrophy, and an atrophy group treated with enalapril on Balb/c mice. After tying a splint to cause atrophy in one of the legs, daily treatment with enalapril intraperitoneally (dissolved in DMSO) at a dose of 10 mg/kg/day was done for 7 days. On the eighth day, the splint was opened and half of the mice were evaluated. Then, in the recovery phase, treatment with enalapril was continued in the remaining mice for 10 days without a splint. At the end of each phase, the mice were examined for the muscle strength of the lower limb muscles, and histological and biochemical analyses were subsequently carried out. The tissue level of the oxidative stress index MDA was evaluated, which showed a significantly lower level in the enalapril group compared to the atrophy group (*P

One of the main causes of death on the globe is cancer. Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors, including PPARα, PPARδ and PPARγ, which are important in regulating cancer cell proliferation, survival, apoptosis, and tumor growth. Activation of PPARs by endogenous or synthetic compounds regulates tumor progression in various tissues. Although each PPAR isotype suppresses or promotes tumor development depending on the specific tissues or ligands, the mechanism is still unclear. PPARs are receiving interest as possible therapeutic targets for a number of disorders. Numerous clinical studies are being conducted on PPARs as possible therapeutic targets for cancer. Therefore, this review will focus on the existing and future uses of PPARs agonists and antagonists in treating malignancies. PubMed, Science Direct, and Scopus databases were searched regarding the effect of PPARs on various types of cancers until the end of May 2023. The results of the review articles showed the therapeutic influence of PPARs on a wide range of cancer on in vitro, in vivo and clinical studies. However, further experimental and clinical studies are needed to be conducted on the influence of PPARs on various cancers.

Abstract The modulating factors within the tumor microenvironment, for example, transforming growth factor beta (TGF-β), may limit the response to chemo and immunotherapy protocols in colorectal cancer (CRC). In the current study, the therapeutic potential of targeting the TGF-β pathway using Pirfenidone (PFD), a TGF-β inhibitor, either alone or in combination with five fluorouracil (5-FU) has been explored in preclinical models of CRC. The anti-proliferative and migratory effects of PFD were assessed by MTT and wound-healing assays respectively. Xenograft models were used to study the anti-tumor activity, histopathological, and side effects analysis. Targeting of TGF-β resulted in suppression of cell proliferation and migration, associated with modulation of survivin and MMP9/E-cadherin. Moreover, the PFD inhibited TGF-β induced tumor progression, fibrosis, and inflammatory response through perturbation of collagen and E-cadherin. Targeting the TGF-β pathway using PFD may increase the anti-tumor effects of 5-FU and reduce tumor development, providing a new therapeutic approach to CRC treatment.

Objective(s): Colon cancer is well-known as a life-threatening disease. Since the current treatment modalities for this type of cancer are powerful yet face some limitations, finding novel treatments is required to achieve better outcomes with fewer side effects. Here we investigated the therapeutic potential of Azurin-p28 alone or along with iRGD (Ac-CRGDKGPDC-amide) as a tumor-penetrating peptide and 5-fluorouracil (5-FU) for colon cancer. Materials and Methods: Inhibitory effect of p28 with or without iRGD/5-FU was studied in CT26 and HT29, as well as the xenograft animal model of cancer. The effect of p28 alone or along with iRGD/5-FU on cell migration, apoptotic activity, and cell cycle of the cell lines was assessed. Level of the BAX and BCL2 genes, tumor suppressor genes [(p53 and collagen type-Iα1 (COL1A1), collagen type-Iα2 (COL1A2)] were assessed by quantitative RT-PCR.Results: These findings show that using p28 with or without iRGD and 5-FU raised the level of p53 and BAX but decreased BCL2, compared with control and 5-FU groups in tissues of the tumor, which result in raising the apoptosis. Conclusion: It seems that p28 may be used as a new therapeutic approach in colon cancer therapy that can enhance the anti-tumor effect of 5-FU.

Abstract Background Adhesion band formation is a common cause of morbidity for patients undergoing surgeries. Anti-inflammatory and anti-fibrotic properties of curcumin, a pharmacologically active component of Curcuma longa, have been investigated in several studies. The aim of this study is to explore the therapeutic potential of curcumin in attenuating post-operative adhesion band (PSAB) formation in both peritoneal and peritendinous surgeries in animal models. Methods Bio-mechanical, histological and quantitative evaluation of inflammation, and total fibrosis scores were graded and measured in the presence and absence of phytosomal curcumin. Results Results showed that phytosomal curcumin significantly decreased severity, length, density and tolerance of mobility of peritendinous adhesions as well as incidence and severity of abdominal fibrotic bands post-surgery. Curcumin may decrease inflammation by attenuating recruitment of inflammatory cells and regulating oxidant/anti-oxidant balance in post-operative tissue samples. Moreover, markedly lower fibrosis scores were obtained in the adhesive tissues of phytosomal curcumin-treated groups which correlated with a significant decrease in quantity, quality and grading of fibers, and collagen deposition in animal models. Conclusion These results suggest that protective effects of phytosomal curcumin against PSAB formation is partially mediated by decreasing inflammation and fibrosis at site of surgery. Further studies are needed to investigate the therapeutic potential of this molecule in preventing PSAB.

Abstract There are significant challenges in developing drug carriers for therapeutic perspective. We have investigated a novel nanocarrier system, based on combining functionalized magnetic nanocomposite with Metal–Organic Frameworks (MOFs). Magnetic nanoparticles modified using biocompatible copolymers may be suitable for delivering hydrophobic drugs, such as cisplatin. Furthermore, compared to polymeric nanocarriers, nanocomposite constructed from zeolitic imidazolate framework-8 (ZIF-8) have demonstrated better drug loading capacity, as well as excellent pH-triggered drug release. Cisplatin-encapsulated Fe3O4@SiO2-ZIF-8@N-Chit-FA has been evaluated to determine the antitumor effects of free cisplatin enhancement in cervical cancer cells. In order to increase the stability of the proposed nanocarrier in aqueous solutions, in addition to the density of functional groups, a nano-chitosan layer was coated on top of the magnetic nanocomposite. It was then added with cisplatin onto the surface of Fe3O4@SiO2-ZIF-8@N-Chit-FA to deliver anticancer treatment that could be targeted using a magnetic field. A mouse isograft model of TC1 cells was used to evaluate the in vivo tumor growth inhibition. In tumor-bearing mice, Fe3O4@SiO2-ZIF-8@N-Chit-FA-cisplatin was injected intraperitoneally, and the targeted delivery was amplified by an external magnet (10 mm by 10 mm, surface field strength 0.4 T) fixed over the tumor site. Based on in vivo results, cisplatin-Loaded Mesoporous Magnetic Nanobiocomposite inhibited the growth of cervical tumors (P

Objective(s): Ulcerative colitis (UC) is a chronic large intestinal condition, for treatment and prevention of which sulfasalazine (SSZ) is used. It functions by helping to reduce inflammation and other disease symptoms within the bowels, but this drug has many side effects. Various novel paths for UC treatment are being studied to solve the difficulties associated with present treatments and to design a more targeted therapy. Hydroxyapatite nanoparticles (HAP-NPs) form an inorganic portion of the natural bone and are primarily used in tissue engineering due to their anti-inflammatory and anti-toxicity character. This study aimed to investigate the anti-inflammatory character of sulfasalazine-containing HAP (SSZ-HAP-NPs) as a potential therapeutic agent.Materials and Methods: The therapeutic efficacy of SSZ-HAP-NPs compared with SSZ as a standard drug was examined in a mouse model of colitis by induction of DSS for 7 days. Drugs were given on the third day and continued for seven days. Colonic mucosal inflammation was evaluated clinically, biochemically, and histologically.Results: Our results showed that SSZ-HAP-NPs clinically improved signs/symptoms more than SSZ, however, it was not statistically significant (P>0.05). Also, SSZ-HAP-NPs diminished histopathological evidence of injury, by decreasing inflammatory responses and balancing oxidative/anti-oxidative markers in colonic tissues (P>0.05). Conclusion: SSZ-HAP-NPs could be more effective than SSZ as standard drug in some laboratory and clinical signs/symptoms and side effects in colitis and this could be a good strategy for future studies to use nanoparticles with more anti-inflammatory effects to develop the efficiency of standard drugs in colitis treatment.

Abstract Mebendazole (MBZ) is an efficacious anthelmintic with known anti-inflammatory and fibrinolytic properties. In this study, we aimed to explore the protective effects of this FDA-approved drug against DSS-induced colitis in a murine model either alone or in combination with Sulfasalazine (SSZ), a standard therapy for ulcerative colitis. We found that MBZ significantly improved colitis disease activity index as assessed by changes in body weight, degree of stool consistency, rectal bleeding, and prolapse. We also found that MBZ ameliorated the colon histopathological score by attenuating crypt loss, mucosal damage, and inflammation score in colitis tissues. Similarly, DSS-induced colon shortening, colon weight loss, and increase in spleen weight were all abrogated in the presence of MBZ. Moreover, MBZ decreased inflammation, possibly by reducing oxidative stress markers, suppressing inflammatory cell infiltration, and down-regulation of inflammatory genes in colon tissues. Furthermore, MBZ potently reduced fibrosis by decreasing collagen deposition and down-regulating pro-fibrotic genes including Col 1a1 and Col 1a2 in colitis tissue homogenates. In conclusion, our study showed that this broad-spectrum anthelminthic could be repurposed as a novel therapy for ulcerative colitis without any observed side effects, however, regarding the concerns about the potential toxicity of MBZ in UC patients, future experiments on MBZ therapy in other models of UC is needed to completely address the toxicity concerns.

Introduction: Cervical cancer is the leading cause of cancer-related death in women, so novel therapeutic approaches are needed to improve the effectiveness of current therapies or extend their activity. In recent decades, graphene analogs, such as Mxene, an emerging class of two-dimensional (2D) graphene analogs, have been drawing considerable attention based on their intrinsic physicochemical properties and performance as potential candidates for tumor therapy, particularly for therapeutic purposes. Here we explored the targeted drug delivery in cervical cancer in in vivo model. Mxene-based nanocarriers are not able to be precisely controlled in cancer treatment.Method: To solve this problem, the titanium carbide-magnetic core-shell nanocarrier (Ti3C2-Fe3O4@SiO2-FA) is also developed to provide synergetic anticancer with magnetic controlling ability along with pH-responsive drug release. A xenograft model of the cervix was used to investigate the effects of Cisplatin alone, or in combination with Ti3C2@FA and Ti3C2@ Fe3O4@SiO2-FA, on tumor growth following histological staining for evaluation of necrosis.Result and Discussion: A significant tumor-growth suppression effect is shown when the Ti3C2-Fe3O4@SiO2-FA nanocarrier is magnetically controlled Cisplatin drug release. It reveals a synergistic therapeutic efficacy used in conjunction with pharmaceuticals (p < .001). According to the in vivo study, the Ti3C2@FA@Cisplatin nanocomposite exhibits less tumor growth than the drug alone or Ti3C2@FA@Cisplatin via increasing necrosis effect (p < .001). Through this study, Mxene nanosheets are expanded for biomedical applications, not only through the fabrication of biocompatible magnetic Mxene nanocomposite but also through the development of functionalization strategies that enable the magnetic Ti3C2 nanocomposite to load high levels of Cisplatin for cervical cancer treatment (242.5%). Hence, Ti3C2-Fe3O4@SiO2-FA nanocarriers would be promising candidates to improve cancer treatment efficiency.

Background: The goal was to assess the specific colon delivery and investigation of synergistic anti-inflammatory effects of the selenium nanoparticle (SeNPs) as a bioactive carrier for oral administration. Material and method: The sulfasalazine (SSZ)- SeNPs functionality and the drug link to SSZ-SeNPs were investigated using chemical methods and characterized by conventional techniques including Fourier transform infrared (FTIR), X-ray diffraction analysis (XRD) analysis, and field emission scanning electron microscopy (FESEM). Dextran sodium sulfate (DSS) was used to induce colitis. Clinical symptoms were monitored every day. Colon samples were evaluated macroscopically and microscopically. The levels of Malondialdehyde (MDA) and the antioxidant markers such as total thiol, superoxide dismutase (SOD) activity, and catalase (CAT) activity of the colon homogenates were also determined. Results: A significant reduction in body weight, colon length and increase in disease activity index, colon and spleen weight/length ratio was observed in colitis group compared to control. Treatment with SSZ-SeNP and SSZ significantly improved these, although there was no significant difference between SSZ-SeNP and SSZ groups. Moreover, evaluation of histological changes including inflammation, crypt loss, mucosal damage and colon fibrosis indicated that treatment by SSZ-SeNP and SSZ significantly improved histological changes and SSZ-SeNP is much more effective than SSZ (P

Background: Epileptic seizures affect the life of noticeable number of people in all over the world. Tanacetum parthenium (TP) is used in traditional medicine. We studied the effects of hydro- ethanolic extract of TP and its n-butanol and aqueous fractions on brain oxidative damage in pentylenetetrazole (PTZ)-induced seizures in mice. Methods: Male mice were divided into: (1) Control; (2) PTZ (100 mg/kg, i.p.); (3-5) hydro-ethanolic extract of TP (50, 100 and 200 mg/kg); (6) n-butanol (NBut) (100 mg/kg) and (7) aqueous (Aq) (100 mg/kg) fractions. Extracts were injected (i.p.) for 3 days and 30 min before PTZ. Latencies in onset of Minimal Clonic Seizures (MCS) and Generalized Tonic-Clonic Seizures (GTCS) as well as biochemical indicators were evaluated. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Conclusion: Results demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Conclusion: Results demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress.

Introduction: Breast cancer is one of the most common cancers and the second leading cause of cancer deaths among women worldwide. There is direct relationship between hypertension and the risk of blood cancer. Since the studies have showed that renin-Angiotensin pathway can be involved in cancer progression, therefore, this study was performed with aim to investigate the effect of angiotensin-converting enzyme inhibitors (ACEI) on survival of breast cancer patients by meta-analysis method. Methods: In this systematic review and meta-analysis, the databases of pubmed, scopus, and web of science were systematically searched with the keywords of Breast cancer, neoplasm, tumor, Angiotensin receptor blockers, Angiotensin converting enzyme inhibitors and survival using OR and AND without a time limit until February 19, 2020. I2 index was used to assess the heterogeneity between the studies. Egger's test was used for assessment of publication bias. Data were analyzed by meta-analysis method using random effects model. Results: In this study, a total of 57708 papers were reviewed and 13 studies were included in this meta-analysis. The results of meta-Analysis showed that based on the random effects model, ACEI had no effect on the survival of patients with breast cancer (HR = 0.1; 95% CI: 12.1 to 0.89; p = 0.99). Conclusion: The results of the studies show that using angiotensin receptor blocker and renin-angiotensin system inhibitors had no effect on survival of patients with breast cancer.

Background: Frequent seizure is followed by overproduction of free radicals and brain oxidative stress. Renin angiotensin system (RAS) has some effects on central nervous system. We designed this research to challenge the effect of captopril as an angiotensin converting enzyme (ACE) inhibitor against brain oxidative stress in pentylenetetrazole (PTZ) -induced seizures in mice. Methods: The groups were including (1) Control (saline); (2) PTZ (100 mg/kg, i.p.), (3-5) PTZ- captopril (Capto) that received three doses of Capto 10, 50 and 100 mg/kg 30 min before PTZ injection. Latency time in the onset minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) were recorded. The level of malondialdehyde (MDA) and total thiol, as well as superoxide dismutase (SOD) and catalase (CAT) activity in the hippocampus and cortex were measured. Results: All doses of captopril postponed the onset of MCS and GTCS. Accumulation of MDA in the brain tissues of PTZ group was higher than control group, while total thiol content and CAT activity were lower. Pretreatment with captopril (100 mg/kg) diminished MDA concentration compared with PTZ group. Captopril (50 and 100 mg/kg) also increased the level of total thiol groups versus PTZ group. Captopril injection (50 and 100 mg/kg) elevated the activity of SOD and CAT in the brain tissues. In addition captopril administration diminished mortality rate caused by PTZ. Conclusion: Findings demonstrated that convulsions caused by PTZ were followed by oxidative stress status in the brain tissues. Pretreatment with captopril attenuated the effect of PTZ on brain tissue oxidative damage.

Objectives: Thymoquinone (TQ) is one of the active ingredients of herbal plants such as Nigella sativa L. (NS) which has beneficial effects on the body. The beneficial effects of TQ on the cardiovascular system have reported. This study aimed to investigate the effect of TQ on cardiac fibrosis and permeability, serum and tissue concentration of inflammatory markers and oxidative stress status in chronic lipopolysaccharide exposure in male rats. Methods: Seventy male Wistar rats were randomly divided into five groups as follows: (1) control; (2) LPS (1 mg/kg/day); (3-5) LPS + TQ with three doses of 2, 5 and 10 mg/kg (n=14 in each group). After 3 weeks, serum and cardiac levels of IL-1β, TNF-α and nitric oxide (NO) metabolites, and cardiac levels of malondialdehyde (MDA), total thiol groups, catalase (CAT) and superoxide dismutase (SOD) activities, permeability of heart tissue (evaluated by Evans blue dye method) and myocardial fibrosis were determined, histologically. Results: LPS administration induced myocardial and perivascular fibrosis and increased cardiac oxidative stress (MDA), inflammatory markers and heart permeability, while, reduced anti-oxidative enzymes (SOD and CAT) and the total thiol group. Administration of TQ significantly attenuated these observations. Conclusion: TQ improved myocardial and perivascular fibrosis through suppression of chronic inflammation and improving oxidative stress status and can be considered for attenuation of cardiac fibrosis in conditions with chronic low-grade inflammation.

BACKGROUND: Subclinical inflammation induced by persistent exposure to lipopolysaccharide (LPS) is found in some clinical conditions such as obesity or diabetes. This study aimed to investigate the effect of recurrent LPS exposure on inflammatory markers, oxidative stress balance and cardiac and renal fibrosis in male rats.METHODS: Male Wistar rats were divided into control and LPS-treated. LPS (10 mg/kg/week) was injected intraperitoneally. After 4 weeks, left ventricles and kidneys were homogenized and stained with hematoxylin and eosin (H&E) and Masson trichrome for histological examination. Serum levels of nitrite, interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured and total thiol, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase were evaluated in the heart and kidney homogenates.RESULTS: Serum inflammatory markers were higher in LPS group than control (nitrite: 37.0 ± 2.2 vs. 25.5 ± 1.9 µmol/l; IL-6: 84 ± 3 vs. 98.0 ± 4.4 pg/ml; TNF-α: 75.5 ± 4.9 vs. 85.3 ± 4.7 pg/ml; respectively, P < 0.050). Evaluation of total thiol concentration (heart: 10.0 ± 0.9 vs. 22.5 ± 1.2; kidney: 7.0 ± 0.5 vs. 27.8 ± 3.1 nmol/g tissue, respectively), catalase (heart: 0.18 ± 0.03 vs. 0.66 ± 0.04; kidney: 0.17 ± 0.03 vs. 0.73 ± 0.03, U/g tissue, respectively) and SOD (heart: 8.01 ± 0.70 vs. 12.3 ± 0.4; kidney: 7.02 ± 0.60 vs. 12.0 ± 0.2, U/g tissue, respectively) showed lower levels in LPS-treated group compared to control; while MDA concentration in LPS group was higher than control (P < 0.05). Histopathological examination in LPS-treated group indicated infiltration of inflammatory cells and more collagen deposition in left ventricle wall and kidney compared to control group.CONCLUSION: We concluded that in clinical conditions with chronic LPS, cardiac and renal fibrosis occurs even in absence of preceding tissue injury due to imbalances in oxidative stress.

Objective: Liver fibrosis is the primary sign of chronic liver injury induced by various causes. Thymoquinone (TQ) is the major ingredient of Nigella sativa with several beneficial effects on the body. In the present study, we aimed to investigate the effect of TQ on liver fibrosis in a lipopolysaccharide (LPS)-induced inflammation in male rats. Materials and methods: Fifty male Wistar rats were randomly divided into five groups (n=10 in each group) as follow: (1) control; (2) LPS (1 mg/kg/day; i.p); (3) LPS+TQ 2 mg/kg/day (i.p) (LPs+TQ2); (4) LPS+TQ 5 mg/kg/day (LPS+TQ5); (5) LPS+ TQ 10 mg/kg/day (LPS+ TQ10). After three weeks, blood samples were taken for evaluation of liver function tests. Then, the livers were harvested for histological evaluation of fibrosis and collagen content and measurement of oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase activity in tissue homogenates. Results: LPS group showed higher levels of fibrosis and collagen content stained by Masson’s trichrome in liver tissue with impaired liver function test and increased oxidative stress markers (p

Thymoquinone (TQ) is the main active ingredient of Nigella sativa seeds with various pharmacological effects. The aim of this study was to investigate the effect of TQ on renal fibrosis and permeability and oxidative stress status in lipopolysaccharide (LPS)-induced inflammation in male rats. Eighty male Wistar rats were divided into 5 groups as follow: control (received normal saline), LPS (1 mg/kg/day), and LPS+TQ (by doses of 2, 5 and 10 mg/kg/day). After three weeks, the biochemical parameters such as blood urea nitrogen (BUN) and creatinine in serum samples, oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase (CAT) activities in renal tissue homogenate and renal permeability (evaluated by Evan’s blue dye method) were measured and renal fibrosis was evaluated, histologically using Masson’s trichrome staining. LPS administration induced renal fibrosis (1.49 ± 0.08 vs. 7.15 ± 0.18%) and significantly increased renal permeability (6.03 ± 1.05 vs. 13.5 ± 1.04 μg evans blue(EB)/g tissue), serum BUN and creatinine levels and oxidative stress marker (MDA) (P < 0.05), while, it reduced anti-oxidative markers including total thiol group, SOD and CAT activities (P < 0.05). Administration of TQ significantly improved these alterations which were dose-dependent in oxidative stress markers, renal permeability (TQ 2, 5 and 10 mg/kg: 10.7 ± 0.3, 9.2 ± 1.4 and 11.5 ± 0.6 μg EB/g tissue; respectively) and fibrosis (TQ 2, 5 and 10 mg/kg: 6.09 ± 0.7, 4.26 ± 0.14 and 2.52 ± 0.08%; respectively). In conclusion, administration of TQ reduced renal fibrosis and permeability and improved oxidative stress status. Thus, TQ can be considered in conditions accompanied with chronic inflammation at least as a part of treatment strategy.

Nigella sativa (NS) (Ranunculaceae) used as a protective and therapeutic traditional medicine. This study evaluates the effect of NS on inflammation-induced myocardial fibrosis, serum and tissue inflammatory markers, and oxidative stress status in male rats. Fifty male Wistar rats were divided into five groups: (1) control; (2) lipopolysaccharide (LPS), 1 mg/kg/day; (3) LPS + NS (hydroalcoholic extract), 100 mg/kg/day; (4) LPS + NS, 200 mg/kg/day; (5) LPS + NS, 400 mg/kg/day (n = 10 in each group). The duration of LPS administration was two weeks. At the end of the experiment, blood samples were taken and ventricles were homogenized and stained for histological evaluation. Serum nitrite levels were lower in LPS group than the control group (22.98 ± 1.03 vs 28.5 ± 0.93 μmol/L), in which they were significantly increased by NS treatment (P < 0.05). Higher levels of heart interlukine-6 (IL-6) and tumor necrosis factor-α (TNF-α) were observed in LPS group compared to the controls (IL-6: 6805 ± 656 vs 4733 ± 691 pg/mL; TNF-α: 6504 ± 501 vs 5309 ± 452 pg/mL), in which they were reduced by NS 400 mg/kg compared to LPS groups (P < 0.05). A significant increment of malondialdehyde and reduction in heart total thiol, superoxide dismutase and catalase concentrations were observed in LPS group (p < 0.05) which significantly restored with treatment by three doses of NS. Histopathological studies showed higher inflammatory cell infiltrates, cardiac fibrosis, and collagen deposition in LPS group, which were reduced by the administration of NS. Treatment by NS reduced myocardial fibrosis in inflammation-induced fibrosis, possibly through improving oxidative/anti-oxidative balance.

التهاب مزمن خفیف (Chronic low-grade inflammation) یافته‌ای پاراکلینیک است که امروزه در بسیاری از بیماری‌های شایع و مهم جوامع بشری مثل چاقی، دیابت، بیماری‌های عصبی و ... مشاهده می‌شود. به همین دلیل، مطالعات مختلفی بر روی علل و اثرات آن بر بدن در شرایط مختلف پاتولوژیک انجام و پیشنهاد شده است که التهاب مزمن خفیف در پاتوژنز ایجاد این بیماری‌ها یا عوارض آن‌ها نقش زیادی دارد. التهاب مزمن خفیف، با افزایش سطح لیپوپلی ‌ساکارید باکتریایی گرم منفی در گردش خون مشخص می‌شود که به دنبال آن، عوامل التهابی نیز افزایش می‌یابد. عوامل مختلفی ممکن است در ایجاد این التهاب نقش داشته باشند و به دنبال آن، التهاب نیز می‌تواند عوارض و عواقبی بر عملکرد قسمت‌های مختلف بدن داشته باشد. در این مقاله‌ی مروری به بررسی این علل و عوارض خواهیم پرداخت.

Background: Renin-angiotensin (Ang)-aldosterone system not only plays a key role in the regulation of circulatory homeostasis, but also it acts as a powerful pro-inflammatory mediator. The aim of this study was to evaluate the effect of captopril (Cap), a known Ang-converting enzyme inhibitor, on inflammation-induced cardiac fibrosis, and heart oxidative stress status in lipopolysaccharide (LPS)-induced inflammation in male rats. Methods: Fifty male rats were randomly divided into five groups control, LPS (1 mg/kg/day), LPS + Cap 10 mg/kg, LPS + Cap 50 mg/kg and LPS + Cap 100 mg/kg. After 2 weeks, blood samples were taken, and hearts were harvested for evaluation of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide metabolite in serum and tissue hemogenate, histopathology (hematoxylin and eosin and Masson's trichrome) and oxidative stress status. Results: Serum IL-6 and TNF-α concentration were higher in LPS group compared to control and Cap reduced them, significantly. Heart TNF-α and IL-6 contents in LPS group were significantly higher than control (P < 0.05). The administration of Cap significantly decreased inflammatory markers level to control (P < 0.05). The higher levels of malondialdehyde and lower antioxidative markers (total thiol, superoxide dismutase, and catalase) in the heart were observed in LPS group and treatment by Cap improved them, dose-dependently. Histopathological study revealed cardiac fibrosis and more collagen content in LPS group which significantly improved by Cap treatment. Conclusions: Treatment by Cap reduced cardiac fibrosis possibly through improving oxidative stress status, and it can be considered to increase cardiac compliance in this condition.