Earlier, we proposed that the ability of folic acid and vitamin B₁₂ to preserve systemic and mitochondrial function after short-term exposure to arsenic may prevent further progression to more permanent injury and pathological changes leading to cell death. To elucidate its mechanism, the present study examined the antiapoptotic efficacy of folic acid and vitamin B₁₂ against short-term arsenic exposure-induced hepatic mitochondria oxidative stress and dysfunction. Sixteen to eighteen weeks old male albino rats weighing 140-150 × g were divided into five groups: Control (A), Arsenic-treated (B), Arsenic + folic acid (C), Arsenic +vitamin B₁₂ (D), and Arsenic + folic acid + vitamin B₁₂ (E). Data generated indicated that folic acid and vitamin B₁₂ separately or in combination can give significant protection against alterations in oxidative stress and apoptotic marker parameters and downstream changes in mitochondria, namely pro-oxidative (NO, TBARS, OH⁻) and antioxidative defense (SOD, CAT, GSH) markers, iNOS protein expression, mitochondrial swelling, cytochrome c oxidase and Ca²⁺-ATPase activity, Ca²⁺ content, caspase-3 activity. Additionally, results of hepatic cell DNA fragmentation, arsenic load of blood, hepatic tissue and urine, and histological observations, all strongly support that both these supplements have efficacy in preventing apoptotic changes and cellular damage. As the mechanisms of actions of both of these supplements are methylation related, a combined application was more effective. Results further reveal new molecular targets through which folic acid and vitamin B₁₂ separately or in combination work to alleviate one critical component of arsenic-induced liver injury: mitochondria dysfunction.

The effect of folic acid and folic acid + vitamin B12 supplementation upon short‐term arsenic‐induced systemic and pancreatic islet cell mitochondria oxidative stress was investigated in male rats. Arsenic trioxide was administered orally at a dose of 3 mg kg body weight−1 day−1 for 30 days, and folic acid and vitamin B12 were administered at a dose of 36 and 0.63 μg kg body weight−1 day−1, respectively, for 30 days. Compared to control, arsenic‐treated group showed a significant increase in the levels of systemic oxidative markers, malondialdehyde (MDA), nitric oxide (NO), and hydroxyl radical (OH−) formation, which were found decreased significantly after supplementation either with folic acid or a combination of folic acid + vitamin B12. Similar supplementations were found effective against arsenic‐induced oxidative marker changes (MDA, NO, and OH−) in pancreatic islet cell mitochondria. Also, low activities of antioxidant defense enzymes such as superoxide dismutase and catalase, and level of antioxidant glutathione, all could regain significantly on supplementations both against systemic and islet cell mitochondria oxidative stress. Results of agarose‐gel electrophoresis of DNA from lymphocytes and islet cells of arsenic‐exposed rats showed DNA smearing, which could be reduced with simultaneous administration either with folic acid or a combination of folic acid + vitamin B12. Significantly, similar supplementations were found effective in increasing the urinary clearance of arsenic. Together, these results indicate that folic acid and vitamin B12 may be effective to reduce the arsenic‐induced damage at molecular target level. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.

This study examined the efficacy of hydroalcoholic extract of dried clove buds, which is rich in phenolic compounds namely eugenol and eugenol derivatives (precursors of flavones, isoflavones and flavonoids), on different primary and secondary osteoporotic marker changes in an ovariectomised (OVX) rat model of osteoporosis. Female Wistar rats were randomly divided into three groups: sham-operated control (A), OVX (B) and OVX plus 50% hydroalcoholic extract of dried clove buds for 4 weeks (C). Results indicated that, compared to control, serum alkaline phosphatase (AP; 48.25%, p < 0.01), serum tartrate-resistant acid phosphatase (TRAP; 63.48%, p < 0.01), urinary calcium (14.70%, p < 0.01), urinary phosphate (50.30%, p < 0.01) and urinary creatinine (122.44%, p < 0.01) were significantly altered in OVX rats. All these altered responses were significantly restored (AP: 27.53%, p < 0.01; TRAP: 33.51%, p < 0.01; calcium: 53.15%, p < 0.01; phosphate: 27.49%, p < 0.01; creatinine: 46.40%, p < 0.01) by supplementation with hydroalcoholic extract of dried clove buds. Results of bone density, bone mineral content, bone tensile strength and histological analysis also showed similar trend of results, which supported initial observations of this study. It is proposed that hydroalcoholic extract of dried clove buds has bone-preserving efficacy against hypogonadal osteoporosis.

The chemoprotective actions of aqueous black tea extract (BTE) against high-fat diet (HFD) (60%)-induced non-alcoholic steatohepatitis (NASH) were examined in Wistar rats of both sexes. The results indicated that the HFD rats had higher concentrations of serum glucose, cholesterol, triglycerides, low-density lipoprotein, very low-density lipoprotein, high-density lipoprotein and bilirubin than the corresponding control rats. The enzymes serum aspartate aminotransferase and alanine aminotransferase, which are indicators of liver function, also exhibited higher levels of activity in HFD rats. BTE extract supplementation was found to correct such steatohepatitis-linked biochemical changes. HFD-induced steatohepatitis was associated with substantial pro-oxidant conditions in rat liver, as evidenced by the higher content of malondialdehyde, nitric oxide production and glutathione depletion, with a concomitant decrease in liver antioxidant status caused by reducing superoxide dismutase and catalase activity. In addition, rats with steatohepatitis showed a significantly higher expression of inducible nitric oxide synthase, caspase-3 activity and DNA fragmentation. BTE reversed the changes in the pro-oxidant and antioxidant status of the liver, and protected against apoptotic, cytogenetic and hepatocellular damage. In summary, these data suggest that nutritional support with antioxidants may be useful in preventing oxidative damage and the progression of NASH.

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