ABSTRACT
BACKGROUND/AIMS: Agriculture and industrial expansion in recent years have resulted in the undue discharge of arsenic into the environment, building arsenic toxicity a major worldwide anxiety. Oxidative stress is considered as the most conspicuous effect of arsenic toxicity. The current study was designed to evaluate the protective ability of sulforaphane (SFN) against arsenic (As) induced hepatotoxicity by activation of PI3K induced Akt and Nrf2 mediated signaling pathway. METHODS: For this purpose, male Wistar rats were randomly distributed into 6 groups of 8 rats each: control, Arsenic (5mg/kg BW), SFN plus Arsenic (20, 40, 80 mg/kg BW; 5mg/kg BW) and Vit. C plus Arsenic (100mg/kg BW; 5mg/kg BW). In this study, we have used spectrophotometry for enzymatic antioxidant assays, western blotting and PCR for protein and gene expression. Microtome for histological study. RESULTS: The arsenic-induced oxidative damage was confirmed by a significant (p<0.05) increase in the levels of ALAD, As concentration and depletion in the antioxidant content. Furthermore, Arsenics treatments significantly (p<0.05) increased the pro-apoptotic marker (Bax) and DNA damage, with decreased Nrf2 protein responsible for liver protection. However, pretreatment with SFN significantly (p<0.05) decreased the levels of ALAD, Arsenic concentration, and brought antioxidant enzymes into normal levels. This was accomplished by inhibition of apoptotic markers via activation of PI3K, Akt and Nrf2 mediated signaling pathway as evident from western blotting and PCR techniques. CONCLUSION: Moreover, SFN pretreatment shield the liver histoarchitecture observed in Arsenic treated groups suggesting prevention of liver toxicity via PI3K/Akt mediated Nrf2 signaling pathways and could possibly provide a protection against Arsenic induced hepatic burden.
Subject(s)
Arsenic/toxicity , Chemical and Drug Induced Liver Injury/prevention & control , Isothiocyanates/pharmacology , Liver/metabolism , NF-E2-Related Factor 2/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Animals , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Liver/pathology , Male , Rats , Rats, Wistar , SulfoxidesABSTRACT
Oxidative stress plays a significant role in the pathophysiology of numerous kidney diseases, generally mediated by reactive oxygen species (ROS). Arsenic (Ar) is known to exert its toxicity through the generation of ROS and inflammation. The current study investigates the protective effects of sulforaphane (SFN) against arsenic-induced renal damage via PI3K/Akt-mediated Nrf2 pathway signaling. Thirty-two male albino Wistar rats were randomly divided into four groups of eight animals each, designated as control, arsenic (Ar), sulforaphane plus Ar (SFN+Ar), and sulforaphane alone (SFN), with oral administration of Ar (5 mg/kg BW) and SFN (80 mg/kg BW) daily for 28 days. Ar administration significantly (P < 0.05) increased the levels of ROS, OHdG, Ar accumulation, and lipid peroxidation, and decreased levels of enzymatic and nonenzymatic antioxidants. Notably, a significant (P < 0.05) increase was observed in markers of apoptosis, DNA damage, TUNEL-positive cells, and dark staining of ICAM-1 in renal tissue with decreased PI3K/Akt/Nrf2 gene expression. The biochemical findings were supported by histopathological and electron microscopy evaluation, which showed severe renal damage in rats treated with Ar. Pretreatment with SFN significantly (P < 0.05) attenuated renal ROS, OHdG, lipid peroxidation, and DNA damage, and increased phase II antioxidants via PI3K/Akt-mediated Nrf2 activation in renal tissue. These results show that dietary supplementation with SFN protects against Ar-induced nephrotoxicity via the PI3K/Akt-mediated Nrf2 signaling pathway in the rat kidney.
