This study elucidates the protective role of Green tea (Camellia sinensis or CS) against arsenic-induced mutagenic DNA-breakage/intestinal (small) damages in female rats. Intestinal epithelial cells receive ingested arsenic initially. Though, the possibility of damages in this tissue is immense and the therapeutic strategies against this damage are of great concern, reports on either issue are scanty. Our earlier study on arsenic-exposed human unveils a link between carcinogenesis and mutagenic DNA damage. Here, we demonstrate that supplementation of CS-extract (10 mg/mL water) with NaAsO2 (0.6 ppm)/100 g b.w. for 28 days to rats offered a significant protection against arsenic-induced oxidative damages to DNA and intestinal (small) tissues by buttressing antioxidant systems. Necrotic and apoptotic damages and their CS-protection are shown in DNA-fragmentation, comet-assay, and histoarchitecture (hematoxylin and eosin and periodic acid-schiff staining) results. Only arsenic exposure significantly decreased intestinal superoxide dismutase, catalase activities, and level of soluble thiol with a concomitant increase in malondialdehyde/conjugated dienes. Alteration of serum necrotic marker lactate dehydrogenase and the metabolic inflammatory marker c-reactive protein also indicate the impairment may be occurring at transcription and/or cellular signal transduction level. In addition, in situ incubation in rat intestinal loop filled for 24 h with NaAsO2 alone (250 µM) or with aqueous CS-extract (250 mg/mL) suggests that small intestinal epithelial cells are significantly protected by CS against arsenic-associated necrotic/mutagenic damages, which is observed in DNA-breakage studies. In conclusion, besides intensifying endogenous antioxidant system, CS polyphenols also offer a direct role on free radical scavenging activity that is associated to the protection from mutagenic DNA-breakages and prevention of tissue necrosis/carcinogenesis generated by arsenic.

In an attempt to develop new herbal therapy, an aqueous extract of the seed of Moringa oleifera was used to screen the effect on arsenic-induced hepatic toxicity in female rat of Wistar strain. Subchronic exposure to sodium arsenite (0.4 ppm/100 g body weight/day via drinking water for a period of 24 days) significantly increased activities of hepatic and lipid function markers such as alanine transaminase, aspartate transaminase, cholesterol, triglycerides, LDL along with a decrease in total protein and HDL. A notable distortion of hepatocellular histoarchitecture was prominent with a concomitant increase in DNA fragmentation following arsenic exposure. A marked elevation of lipid peroxidation in hepatic tissue was also evident from the hepatic accumulation of malondialdehyde and conjugated dienes along with suppressed activities in the antioxidant enzymes such as superoxide dismutase and catalase. However, co-administration of aqueous seed extract of M. oleifera (500 mg/100 g body weight/day for a period of 24 days) was found to significantly prevent the arsenic-induced alteration of hepatic function markers and lipid profile. Moreover, the degeneration of histoarchitecture of liver found in arsenic-treated rats was protected along with partial but definite prevention against DNA fragmentation induction. Similarly, generation of reactive oxygen species and free radicals were found to be significantly less along with restored activities of antioxidant enzymes in M. oleifera co-administered group with comparison to arsenic alone treatment group. The present investigation offers strong evidence for the hepato-protective and antioxidative efficiencies of M. oleifera seed extract against oxidative stress induced by arsenic.

The present study elucidated the protective role of vitamin B(12) with folic acid against arsenic-induced hepatotoxicity in female rats. Ingestion of sodium-arsenite- contaminated water [0.4 ppm/100 g body weight (b.w.)/day] in combination with vitamin B(12) plus folic acid (0.07 and 4.0 μg, respectively/100 g b.w./day) for 24 days to Wistar rats offered a significant protection against alone arsenic-induced distorted liver function, damaged histoarchitecture, elevated oxidative stress, and DNA fragmentation of hepatic tissues. Arsenic only exposure decreased hepatic superoxide dismutase (SOD), catalase activities, and the level of nonprotein-soluble thiol (NPSH), with a concomitant increase in thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CDs) in the liver. Vitamin supplementation restrained the increase of TBARS and CDs by restoring catalase, SOD, and NPSH levels. Restricted generation of free radicals may be correlated to the protection of DNA stability and hepatic morphology. This study explains the decisive role of vitamin B(12) with folic acid to ameliorate arsenic-mediated liver injuries.

Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.

Arsenic is an environmental toxicant, free-radical generator, carcinogenic agent, and aging promoter. Recently, blood samples were analyzed from individuals (control- male 12, female 13; arsenic-exposed- male 16, female 14; and exposed to ≥100 μg/L As, ≥10 y) with dermatological symptoms in few affected villages in Eastern India to unravel their hematopoietic, metabolic, and antioxidant profiles. White blood cells recovered from buffy coat were used for DNA fragmentation test. Present observation suggests that significant number of individuals developed pigmentation and palmoplantar hyperkeratosis with black-brownish patch on their body and many of those developed carcinomas. Hematopoietic data show a significant increase in eosinophil and decrease in monocyte count in either sex. Though insignificant, an increase in neutrophil in female and lymphocyte count in male arsenic-exposed individuals are supported by the earlier report on sex dimorphic immune sensitization. Significant increase in serum alanine transaminase in both sexes and bilirubin only in male suggests the eventuality of hepatic disintegration. Arsenic exposure significantly decreased serum amylase in female. A significant decrease in antioxidant components like catalase, soluble thiol, and recently recognized uric acid worsened the situation by generating free radicals as observed in significant rise in malondialdehyde level, which finally increased DNA fragmentation and arsenic-associated mutagenesis and carcinogenesis. This could attribute to lowering in immune competence and related necrotic and/or apoptotic manifestations.