Arsenic-induced hepatic mitochondrial toxicity in rats and its amelioration by diallyl trisulfide

Abstract

The present investigation was aimed to investigate the possible protective role of diallyl trisulfide (DATS) against arsenic (As)-induced hepatic mitochondrial toxicity in rats. Mitochondria were isolated from the liver tissue of rats from all the groups. Lipid profile, lipid peroxidation, antioxidant enzyme activities, hepatic function enzymes, mitochondrial swelling, cytochrome c oxidase activity, mitochondrial Ca(+)-ATPase and Na(+)/K(+)-ATPase activity, mitochondrial calcium content and mitochondrial enzyme activities were measured. Short-term As exposure (5 mg/kg bw/d for 28 d) caused liver damage as evidenced by changes in activities of liver enzymes. The effects of As were coupled with enhanced reactive oxygen species generation, mitochondrial swelling, inhibition of cytochrome c oxidase, complex I-mediated electron transfer, decreased Ca(2+)-ATPase and Na(+)/K(+)-ATPase activity, a reduction in mitochondrial calcium content, changes in indices of hepatic mitochondrial oxidative stress, significant increase in mitochondrial lipid peroxidation products and alterations in mitochondrial lipid profile. Significant decreases in mitochondrial antioxidants and tricarboxylic acid cycle enzymes were also found in the liver mitochondria of As-induced hepatic mitochondrial toxicity in rats. As also increased hepatic caspase-3 activity and DNA fragmentation. All these apoptosis-related molecular changes caused by As could be alleviated by supplementation with DATS, which likely suggests a protective role against As-induced hepatotoxic changes and hepatic mitochondrial toxicity. The protective effect of DATS on the liver mitochondria was evidenced by altering all the changes induced by As. Free radical scavenging and metal chelating activities of DATS may be the mechanism, responsible for the protective action against As-induced mitochondrial damage in liver.

Aqueous Extract of Carica Papaya Linn Roots Halts Sodium Arsenite-Induced Renal Inflammation through Inhibiting Adenosine Deaminase, 8-Hydroxy-2′-Deoxyguanosine, C-Reactive Protein and Inducible Nitric Oxide Synthase Activity

“…Vitamin C administration also reduced the levels of arsenic in the tissues compared to the arsenic-only exposed rats. These results are in accordance with results reported by (48) which showed that arsenic dispersal in tissues depends on the route of administration and its form.…”

Biochanin A Ameliorates Arsenic-Induced Hepato- and Hematotoxicity in Rats

“…BCA, a natural isoflavonoid, has been observed to have chelating and antioxidant properties in the presence of transition metal ions due to the orientation of its functional groups [25]. It is well established that arsenic induces alterations in the function of hepatic machinery in both experimental and human studies [26,27]. Hence, in this study, the therapeutic potential of BCA was compared with selenium on arsenic hepatotoxicity and examined in rats with reference to hepatic markers, oxidative stress parameters, lipid profiles, hematological variables, and liver histology.…”

The Role of Reactive Oxygen Species in Arsenic Toxicity

“…Some antioxidants decrease intracellular ROS levels via inhibiting mitochondrial respiratory chain complex I (e.g., metformin) [203]. Others present a protective role against arsenic-induced toxicity by regulating apoptosis-related molecular changes (e.g., diallyl trisulfide) [204,205]. Different types of antioxidants used for rescuing arsenic toxicity and their possible mechanisms are listed in Table 2.…”