Peptides from Liza aurata: Natural Source Attenuate Paracetamol Induced Nephrotoxicity by Modulation of the Inflammatory Response and DNA Damage

The present study investigates the nephroprotective and the molecular mechanisms effects of Liza aurata protein hydrolysates (LAPHs) against paracetamol induced nephrotoxicity and oxidative stress in rats. Oxidative stress as evident by increased malondialdehyde, hydrogen peroxide, advanced oxidation protein product, protein carbonyl, with significant decrease in non protein thiol and glutathione contents, as well as catalase, superoxide dismutase, and glutathione reductase activities. Paracetamol triggered inflammatory response by inducing tumor necrosis factor-α (TNF-α), with the increased expression of cyclooxygenase-2 (Cox-2). Paracetamol also increased alkaline phosphatase (ALP) and lactate deshydrogenase (LDH) activities, along with an increase in blood urea nitrogen, creatinine, low density lipoprotein cholesterol, and total bilirubin levels. LAPHs were found to decrease leakage of LDH and ALP activity and attenuate the increase in biochemical parameters resulted in a subsequent recovery towards normalization. The biochemical parameters and histopathological observation were correlated by regulation of Cox-2, and TNF-α expression. PH-LA, which presented the highest antioxidant and antiinflammatory activities, was fractionated by G-25 chromatography into five fractions. F2 and F4 which exhibited the highest anti-inflammatory and antioxidant activities, respectively, were further fractionated by reverse phase-high performance liquid chromatography. Our findings claimed that PH-LA can be used in preventing and treating many health problems without any side effects and can be applied in the field of nutraceuticals