Hesperidin protects against the chlorpyrifos‐induced chronic hepato‐renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy, and up‐regulation of PARP‐1/VEGF

Abstract

In this study, we investigated the effects of hesperidin (HSP) on oxidants/antioxidants status, inflammation, apoptotic, and autophagic activity in hepato-renal toxicity induced by chronic chlorpyrifos (CPF) exposure in rats. We used a total of 35 male albino rats in five groups of seven: control, HSP 100, CPF, CPF + HSP50, and CPF + HSP100. After rats were sacrificed, blood, liver, and kidney samples were collected.Serum levels of aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP), creatinine, and urea were tested. Then, contents of the superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GPx), and glutathione (GSH) were measured to detect the level of oxidative stress in rat liver and renal tissues. We measured inflammatory and autophagy markers of chlorpyrifos induced oxidative stress in the liver and kidney tissues including TNF-α, iNOS, IL-1 β, COX-2, NF-κB, MAPK14, and Beclin-1 using ELISA. Histopathological findings were also examined followed by immunohistochemical determination of 8-OHdG expression. Real-time PCR (RT-PCR) was used to examine Cas-3, Bax, Bcl-2, PARP-1, and VEGF, which are associated with apoptosis, autophagy, DNA, and endothelial damage, respectively. In addition, PARP-1 activity was supported by western blot and immunofluorescence, VEGF activity was supported by western blot methods. Treatment with HSP reduced the effect of CPF on ALT, AST, ALP, and total proteins, and increased its effect on tissue antioxidants. PARP/VEGF, apoptotic, pro-apoptotic, anti-apoptotic, and autophagic gene expressions were regulated, and Caspase-3 and Bax expressions were decreased; Bcl-2 expression increased in both the liver and kidney samples, and positivity of 8-OHdG and PARP-1 were reduced in the CPF plus

Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy

“…Endogenous FoxO1 is a key regulator of autophagy in neurons (Vidal et al., 2012 ). In addition, studies have shown that Beclin‐1 may be involved in the activation of Caspase‐3 (Küçükler et al., 2021 ). Bcl‐2 negatively regulates autophagy by inhibiting Bax and blocking Beclin‐1 (Lindqvist et al., 2014 ), indicating that there is mutual crosstalk between autophagy and apoptosis.…”

Plant Flavonoids on Oxidative Stress-Mediated Kidney Inflammation

“…SA-mediated increase in kidney 8-OHdG was reduced upon treatment with hesperidin, thereby exerting nephroprotective effects [ 89 ]. Hesperidin reduces CPF-induced hepatorenal toxicity by reducing 8-OHdG levels and regulating PARP/VEGF genes at biochemical, cellular, and molecular levels [ 90 ]. Similarly, AA intoxication can significantly increase 8-OHdG, while administration of hesperidin improves the concentration and activities of antioxidant biomarkers and decreases the expression level of 8-OHdG in kidney tissue [ 91 ].…”

“…Administration of doses 1 and 10 mg/kg showed no significant improvement, while 75, 100, and 150 mg/kg showed significant inhibition of cell death, inflammation, and oxidative stress in kidney injury models [ 73 , 74 , 75 , 76 , 77 ]. Hesperidin was administered at five different doses (10, 25, 50, 100, and 200 mg/kg) [ 89 , 90 , 91 , 117 , 118 , 119 ]. All doses affected protein and mRNA expression levels of TNF-α, IL-1β, NF-κB, SOD, MDA, and GSH.…”

Evaluation of the Levels of Metalloproteinases as well as Markers of Oxidative Stress and Apoptosis in Lung Tissues After Malathion and Rutin Administrations to Rats

“…Moreover, it was observed that decreased GSH levels probably caused a further increase in ROS levels and that these aggressive molecules damaged the membranes of lung tissue cells, causing lipid peroxidation, thereby increasing MDA levels. Previous studies have reported that different flavonoids applied against various pesticide groups alleviate oxidative stress and alleviate the toxic effects of these compounds [31,32]. In our study, it was determined that RUT treatment suppressed oxidative stress by providing the regeneration of GSH, whose levels were significantly reduced by MLT, and by preventing lipid peroxidation.…”