Betaine Protects Mice from Cardiotoxicity Triggered by Sodium Arsenite Through Antioxidative and Anti-inflammatory Pathways.

NaAsO2 is known as a harmful pollutant all over the world, and many chronic heart diseases can be attributed to its prolonged exposure in NaAsO2-contaminated water. Therefore, considering the anti-inflammatory and antioxidant effects of betaine (BET), in this study, our team investigated the cardioprotective effects of this phytochemical agent on sodium arsenite (NaAsO2)-induced cardiotoxicity. Forty male mice were randomly divided into 4 groups: (I) Control; (II) BET (500 mg/kg); (III) NaAsO2 (50 ppm); and (IV) NaAsO2 + BET. NaAsO2 was given to the animals for 8 weeks, but BET was given in the last two weeks. After decapitation, inflammatory factors and biochemical parameters were measured, and Western blot analyses were performed. BET decrease the activity level of alanine aspartate aminotransferase, creatine kinase MB, thiobarbituric acid reactive substances level, inflammatory factors (tumor necrosis factor-α) content, and nuclear factor kappa B expression. Furthermore, BET increased cardiac total thiol and activity levels of catalase, superoxide dismutase, and glutathione peroxidase and nuclear factor erythroid-2 expression. Hence, the administration of BET ameliorated the deleterious effects stemming from the imbalance of oxidative and antioxidant pathways and histopathological alterations observed in NaAsO2-intoxicated mice, thereby attenuating oxidative stress-induced damage and inflammation.

Metformin alleviates sodium arsenite-induced hepatotoxicity and glucose intolerance in mice by suppressing oxidative stress, inflammation, and apoptosis.

BACKGROUND: Epidemiological studies have shown that exposure to sodium arsenite (NaAsO2) causes diabetes and hepatotoxicity. Metformin (MET), an oral hypoglycemic agent, has long been used in diabetes therapy. In addition, MET has been shown to have hepatoprotective effects. In this study, we investigated the effects of MET on NaAsO2-induced hepatotoxicity and glucose intolerance in mice. METHODS: Mice were divided into four groups: Groups I and II received distilled water and NaAsO2 (10 mg/kg, p.o.) for five weeks, respectively. Groups III and IV were treated with NaAsO2 (10 mg/kg, p.o.) for three weeks, followed by MET (125 and 250 mg/kg, p.o.) for the last two weeks before NaAsO2. A glucose tolerance test was performed on day 35. The serum and tissue parameters were also evaluated. RESULTS: Histopathological examination revealed NaAsO2-induced liver and pancreatic damage. NaAsO2 caused hyperglycemia, glucose intolerance, and a significant increase in liver function enzymes. Administration of NaAsO2 significantly reduced hepatic superoxide dismutase, catalase, glutathione peroxidase, and total thiol levels and increased the content of reactive thiobarbituric acid substances. In addition, it led to an increase in liver nitric oxide levels and protein expression of tumor necrosis factor-α, nuclear factor kappa B, and cysteine-aspartic proteases-3. In contrast, treatment with MET (250 mg/kg) significantly improved NaAsO2-induced biochemical and histopathological changes. CONCLUSION: Our findings suggest that the significant effects of MET against NaAsO2-induced hepatotoxicity and glucose intolerance may be exerted via the regulation of oxidative stress, followed by suppression of inflammation and apoptosis.

Hepatoprotective and anti-hyperglycemic effects of ferulic acid in arsenic-exposed mice.

Arsenic is a toxic metalloid that increases the risk of hepatotoxicity and hyperglycemia. The objective of the present study was to assess the effect of ferulic acid (FA) in mitigating glucose intolerance and hepatotoxicity caused by sodium arsenite (SA). A total of six groups including control, FA 100 mg/kg, SA 10 mg/kg, and groups that received different doses of FA (10, 30, and 100 mg/kg), respectively just before SA (10 mg/kg) for 28 days were examined. Fasting blood sugar (FBS) and glucose tolerance tests were conducted on the 29th day. On day 30, mice were sacrificed and blood and tissues (liver and pancreas) were collected for further investigations. FA reduced FBS and improved glucose intolerance. Liver function and histopathological studies confirmed that FA preserved the structure of the liver in groups received SA. Furthermore, FA increased antioxidant defense and decreased lipid peroxidation and tumor necrosis factor-alpha level in SA-treated mice. FA, at the doses of 30 and 100 mg/kg, prevented the decrease in the expression of PPAR-γ and GLUT2 proteins in the liver of mice exposed to SA. In conclusion, FA prevented SA-induced glucose intolerance and hepatotoxicity by reducing oxidative stress, inflammation, and hepatic overexpression of PPAR-γ and GLUT2 proteins.

Neuroprotective effects of dimethyl fumarate against manic-like behavior induced by ketamine in rats.

Medications for treating bipolar disorder (BD) are limited and can cause side effects if used chronically. Therefore, efforts are being made to use new agents in the control and treatment of BD. Considering the antioxidant and anti-inflammatory effects of dimethyl fumarate (DMF), this study was performed to examine the role of DMF on ketamine (KET)-induced manic-like behavior (MLB) in rats. Forty-eight rats were randomly divided into eight groups, including three groups of healthy rats: normal, lithium chloride (LiCl) (45 mg/kg, p.o.), and DMF (60 mg/kg, p.o.), and five groups of MLB rats: control, LiCl, and DMF (15, 30, and 60 mg/kg, p.o.), which received KET at a dose of 25 mg/kg, i.p. The levels of total sulfhydryl groups (total SH), thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-α), as well as the activity of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the prefrontal cortex (PFC) and hippocampus (HPC), were measured. DMF prevented hyperlocomotion (HLM) induced by KET. It was found that DMF could inhibit the increase in the levels of TBARS, NO, and TNF-α in the HPC and PFC of the brain. Furthermore, by examining the amount of total SH and the activity of SOD, GPx, and CAT, it was found that DMF could prevent the reduction of the level of each of them in the brain HPC and PFC. DMF pretreatment improved the symptoms of the KET model of mania by reducing HLM, oxidative stress, and modulating inflammation.

Epicatechin ameliorative effects on methotrexate-induced hepatotoxicity in mice.

BACKGROUND: Due to the fact that methotrexate is widely used both as an immunosuppressive drug and as a chemotherapy agent, many studies are needed to reduce the side effects of this drug on non-target organs. PURPOSE: This study was designed to investigate the effects of epicatechin (Epi) on MTX (methotrexate)-induced hepatotoxicity in mice. RESEARCH DESIGN: After 1 week for adaptation, we randomly divided 42 male Naval Medical Research Institute mice into six groups: (I) control; (II) Epi (100 mg/kg, po); (III) MTX (20 mg/kg, i.p.) on the fifth day; and (IV, V, and VI) Epi (25, 50, and 100 mg/kg, po) + MTX (20 mg/kg, i.p.) on the fifth day. At day 10, the mice were sacrificed and serum factors, oxidative stress markers, and inflammatory cytokines were measured. RESULTS: MTX increased activity level of serum enzymes (alanine aminotransferase and aspartate aminotransferase), lipid peroxidation marker (malondialdehyde), and inflammatory factors including interleukin-1 beta, tumor necrosis factor-alpha, and nitric oxide. Furthermore, MTX decreased glutathione level and activity level of catalase, superoxide dismutase, and glutathione peroxidase. Epi was able to reduce the destructive effects of oxidative/antioxidant system imbalance and inflammatory reactions and also histopathological damage in MTX intoxicated mice. Epi pretreatment reduced liver dysfunction by improving the antioxidant defense system, anti-inflammatory effects, and alleviation of histopathological damage in MTX hepatotoxicity. CONCLUSIONS: Accordingly, Epi can be used as a therapeutic agent in hepatotoxicity associated with MTX chemotherapy.