Glycine alleviated diquat-induced hepatic injury via inhibiting ferroptosis in weaned piglets

Abstract

Objective:The beneficial effects of glycine were tested in piglets with diquat-induced hepatic injury.Methods: Thirty-two piglets were assigned by a 2 × 2 factorial experimental design including glycine supplementation and diquat challenge. After 3 weeks of feeding with a basic diet or a 1% glycine supplemented diet, piglets were challenged with diquat or saline. After 1 week later, the piglets were slaughtered and samples were collected. Results:Our results indicated that glycine alleviated diquat induced morphological hepatic injury, decreased the activities of plasma alanine aminotransferase, aspartate aminotransferase and glutamyl transpeptidase in the piglets under diquat challenge, and increased total antioxidantive capacity and antioxidative enzyme activity significantly. Adding with glycine enhanced the concentrations of hepatic adenosine triphosphate and adenosine diphosphate. Transmission electron microscope observation showed that diquat induced clear hepatocytes ferroptosis and its effect could be alleviated by glycine to a certain degree. Moreover, glycine significantly affected mRNA and protein expression of ferroptosis-related signals in the liver. Conclusion:These results demonstrated that glycine attenuated liver damage via inhibiting ferroptosis.

Melatonin Ameliorates Diquat-Induced Testicular Toxicity via Reducing Oxidative Stress, Inhibiting Apoptosis, and Maintaining the Integrity of Blood-Testis Barrier in Mice

“…Hence, it is necessary to also verify whether melatonin protects the testes from diquat-induced oxidative stress by regulating SIRT1. Meanwhile, other studies suggest that diquat induces lipid peroxidation [ 61 ], in which hepatocytes and intestinal mucosa ferroptosis were caused following the treatment of piglets for seven days, via regulating the expression of ferroptosis mediators (transferrin receptor protein 1, heat shock protein beta 1, solute carrier family 7 member 11, and glutathione peroxidase 4) [ 62 , 63 , 64 ]. It would, therefore, be of interest to determine whether melatonin reverses testis injury following diquat exposure in a ferroptosis-associated manner.…”

Glycine Alleviated Intestinal Injury by Inhibiting Ferroptosis in Piglets Challenged with Diquat

“…Some studies have shown that supplementation of glycine in the diet can increase intestinal GSH content, enhance the intestinal antioxidant level and effectively relieve oxidative stress in mice [ 36 , 37 ]. Moreover, Hua et al found that dietary glycine could increase the activities of T-AOC, GSH-PX, and GSH in the liver, reduce the content of MDA, and alleviate the oxidative stress induced by diquat injection in piglets [ 38 ]. This further illustrated that glycine may improve intestinal antioxidant capacity by increasing the GSH content [ 30 , 33 ].…”

“…Consistent with the results of many studies, it was found that the expression of the GPX4 gene could inhibit iron death and alleviate cell damage [ 43 , 44 , 45 ]. Xu et al have shown that dietary glycine can effectively inhibit the expression of TFR1, a key gene of ferroptosis, and promote the expression of GPX4, thereby alleviating liver injury induced by diquat [ 38 ]. These results suggested that dietary glycine can enhance the synthesis of GPX4, inhibit the occurrence of ferroptosis, and then protect the gut from the damage caused by ferroptosis.…”

Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications

“…Diquat is a selective herbicide that can induce oxidative stress, karyolysis, karyopyknosis, and changes in hepatic cord arrangement in piglets [ 124 ]. Recent studies showed that holly polyphenols extracts (HPE) [ 124 ] and glycine [ 125 ] could alleviate diquat-induced liver injury by targeting ferroptosis. Mechanistically, they both enhanced GPX4 expression, and HPE also inhibited the transfer of Fe 3+ by decreasing TFR1 abundance [ 124 , 125 ].…”