Oxidative stress is thought to be involved in lead-induced toxicity. The aim of this study was to investigate the possible protective role of naringenin on lead-induced oxidative stress in the liver and kidney of rats. In the present investigation, lead acetate (500 mg Pb/L) was administered orally for 8 weeks to induce hepatotoxicity and nephrotoxicity. The levels of hepatic and renal markers such as alanine aminotransferase, aspartate aminotransferase, urea, uric acid, and creatinine were significantly (P < 0.05) increased following lead acetate administration. Lead-induced oxidative stress in liver and kidney tissue was indicated by a significant (P < 0.05) increase in the level of maleic dialdehyde and decreased levels of reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase. Naringenin markedly attenuated lead-induced biochemical alterations in serum, liver, and kidney tissues (P < 0.05). The present study suggests that naringenin shows antioxidant activity and plays a protective role against lead-induced oxidative damage in the liver and kidney of rats.

Objectives:Oxidative stress with subsequent lipid peroxidation (LP) has been suggested as a mechanism for lead-induced toxicity. The current study was carried out to evaluate antioxidant activity of hesperetin against lead acetate-induced oxidative stress.Materials and Methods:The male rats were treated with hesperetin in combination with lead acetate (500 mg/L).Results:The results indicated that hesperetin alone did not induce any significant changes in the biochemistry of serum, liver, and kidney tissues. On the other hand, lead-induced oxidative stress as indicated by significant changes in serum biochemical parameters, including increased lipid peroxide and decreased reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels in liver and kidney tissues. Hesperetin succeeded in improving these biochemical parameters towards the normal values of control.Conclusions:It suggests that hesperetin shows antioxidant activity and plays a protective role against lead-induced oxidative damage in liver and kidney of rats.

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Introduction: Ubiquitin-Proteasome System (UPS) has been validated as a novel anticancer drug target in the past 20 years. The UPS contains two distinct steps: ubiquitination of a substrate protein by ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin ligase (E3), and substrate degradation by the 26S proteasome complex. The E3 enzyme is the central player in the ubiquitination step, and has a wide range of specific substrates in cancer cells, offering great opportunities for discovery and development of selective drugs. Areas covered: This review summarizes the recent advances in small molecule inhibitors of E1s, E2s, and E3s, with a focus on the latest patents (from 2015 to 2018) of E3 inhibitors and modulators. Expert opinion: One strategy to overcome limitations of current 20S proteasome inhibitors is to discover inhibitors of the upstream key components of the UPS, such as E3 enzymes. E3s play important roles in cancer development and determine the specificity of substrate ubiquitination, offering novel target opportunities. E3 modulators could be developed by rational design, natural compound or library screening, old drug repurposes, and application of other novel technologies. Further understanding of mechanisms of E3-substrate interaction will be essential for discovering and developing next generation E3 inhibitors as effective anticancer drugs.