2,4-Dichlorophenoxyacetic acid induced hepatic and renal toxicological perturbations in rat model: Attenuation by selenium supplementation

Abstract

2,4-Dichlorophenoxyacetic acid (2,4-D) is a commercially used herbicide to manage broadleaf weeds that have various toxicological and ecological effects. In view of ever-escalating use of 2,4-D, risk assessment becomes mandatory to ensure the safety of both human health and the ecosystem. Oxidative injury has been expected as a possible mechanism implicated in 2,4-D toxicity. The present study was planned and conducted to explore the antioxidant potential of selenium (Se) supplementation to moderate the 2,4-D hepatic and renal toxicity in a rat model. The rats were randomly assigned to four equal groups and treated via oral gavage for a period of 4 weeks. Group I: received deionized water as a vehicle, group II: received 2,4-D (150 mg−1 kg−1 day−1), group III: received Se supplement (1 mg−1 kg−1 day−1), and group IV: received 2,4-D (150 mg−1 kg−1 day−1) and Se supplement (1 mg−1 kg−1 day−1) simultaneously. After 4 weeks of administration, 2,4-D induced toxicity was observed, as manifested by disrupted levels of plasma urea, creatinine, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Further, 2,4-D caused a considerable increase in tissue malondialdehyde (MDA) levels and decreased activity of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione reductase. Se supplementation exhibited its antioxidant properties by significantly improving urea, creatinine, ALP, AST, and ALT, and MDA levels and antioxidant enzyme activities. In conclusion, the results suggest that 2,4-D induced hepatic and renal toxicities were attenuated by Se supplementation probably owing to its antioxidant properties.

2,4-D Herbicide-Induced Hepatotoxicity: Unveiling Disrupted Liver Functions and Associated Biomarkers

“…This effect was observed in rats receiving doses of 5 mg/kg of Désormone Lourd (600 g/L 2,4-D) for 4 weeks, resulting in a decrease in hepatic GSH levels and the activity of SOD, CAT, GPx, and GST [ 33 ]. Toxicity studies conducted with the active ingredient in rats identified similar results, further supporting that this effect is attributed to the active ingredient [ 71 , 74 ].…”

“…This leads to an increase in AST and ALT activity and levels in the blood, making them sensitive markers of liver damage [ 145 ]. Shafeeq and Mahboob (2021) demonstrated that rats receiving 150 mg/kg/day of 2,4-D for 4 weeks showed increased levels of AST, ALT, and alkaline phosphatase (ALP) [ 74 ]. The increase in the enzymatic activity of these three markers was also observed in zebrafish larvae at 120 hpf when treated with 2.5 mg/L of 2,4-D for two days [ 4 ].…”

“…Oxidative stress plays a significant role in the hepatotoxicity induced by 2,4-D [ 32 , 33 , 74 ]. Therefore, chemical compounds with antioxidant properties are being tested in hepatoprotection assays, aiming to reduce the damage caused by the herbicide ( Table 3 ).…”

“…Studies in rats have demonstrated that supplementation with selenium (Se) attenuates the 2,4-D-induced hepatotoxicity. This protection is indicated by the reduction in markers of liver function (AST, ALT, ALP), levels of MDA, and histopathological liver damage, and also by the improvement in the activity of hepatic antioxidant enzymes (CAT, GR, SOD, and GPx) [ 32 , 74 ]. Similar results were also found in rats supplemented with magnesium (Mg) [ 71 ].…”

“…Similar results were also found in rats supplemented with magnesium (Mg) [ 71 ]. Se and Mg play essential roles as enzymatic cofactors in antioxidant systems (e.g., for GPx activation and activity), contributing to cell protection against oxidative damage [ 71 , 74 ].…”