Glutathione (GSH), a tripeptide particularly concentrated in the liver, is the most important thiol reducing agent involved in the modulation of redox processes. It has also been demonstrated that GSH cannot be considered only as a mere free radical scavenger but that it takes part in the network governing the choice between survival, necrosis and apoptosis as well as in altering the function of signal transduction and transcription factor molecules. The purpose of the present review is to provide an overview on the molecular biology of the GSH system; therefore, GSH synthesis, metabolism and regulation will be reviewed. The multiple GSH functions will be described, as well as the importance of GSH compartmentalization into distinct subcellular pools and inter-organ transfer. Furthermore, we will highlight the close relationship existing between GSH content and the pathogenesis of liver disease, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), chronic cholestatic injury, ischemia/reperfusion damage, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatocellular carcinoma. Finally, the potential therapeutic benefits of GSH and GSH-related medications, will be described for each liver disorder taken into account.

https://www.mdpi.com/2076-3921/10/3/364/pdf

Changes in Glutathione Content in Liver Diseases: An Update

The inhibition of NFкB signaling and inflammatory response as a strategy for blunting bile acid-induced hepatic and renal toxicity.

The crucial role of oxidative stress in non-alcoholic fatty liver disease-induced male reproductive toxicity: the ameliorative effects of Iranian indigenous probiotics

Lithium (Li+) is prescribed against a wide range of neurological disorders. Besides its excellent therapeutic properties, there are several adverse effects associated with Li+. The impact of Li+ on renal function and diabetes insipidus is the most common adverse effect of this drug. On the other hand, infertility and decreased libido is another complication associated with Li+. It has been found that sperm indices of functionality, as well as libido, is significantly reduced in Li+-treated men. These adverse effects might lead to drug incompliance and the cessation of drug therapy. Hence, the main aims of the current study were to illustrate the mechanisms of adverse effects of Li+ on the testis tissue, spermatogenesis process, and hormonal changes in two experimental models. In the in vitro experiments, Leydig cells (LCs) were isolated from healthy mice, cultured, and exposed to increasing concentrations of Li+ (0, 10, 50, and 100 ppm). In the in vivo section of the current study, mice were treated with Li+ (0, 10, 50, and 100 ppm, in drinking water) for five consecutive weeks. Testis and sperm samples were collected and assessed. A significant sign of cytotoxicity (LDH release and MTT assay), along with disrupted testosterone biosynthesis, impaired mitochondrial indices (ATP level and mitochondrial depolarization), and increased biomarkers of oxidative stress were detected in LCs exposed to Li+. On the other hand, a significant increase in serum and testis Li+ levels were detected in drug-treated mice. Moreover, ROS formation, LPO, protein carbonylation, and increased oxidized glutathione (GSSG) were detected in both testis tissue and sperm specimens of Li+-treated mice. Several sperm anomalies were also detected in Li+-treated animals. On the other hand, sperm mitochondrial indices (mitochondrial dehydrogenases activity and ATP levels) were significantly decreased in drug-treated groups where mitochondrial depolarization was increased dose-dependently. Altogether, these data mention oxidative stress and mitochondrial impairment as pivotal mechanisms involved in Li+-induced reproductive toxicity. Therefore, based on our previous publications in this area, therapeutic options, including compounds with high antioxidant properties that target these points might find a clinical value in ameliorating Li+-induced adverse effects on the male reproductive system.

/pdf/the-role-of-mitochondrial-impairment-and-oxidative-stress-in-3vtzi89c7n.pdf

The Role of Mitochondrial Impairment and Oxidative Stress in the Pathogenesis of Lithium-Induced Reproductive Toxicity in Male Mice

Cholestasis is a clinical complication with different etiologies. The liver is the primary organ influenced in cholestasis. Renal injury is also a severe clinical complication in cholestatic/cirrhotic patients. Several studies mentioned the importance of oxidative stress and mitochondrial impairment as two mechanistically interrelated events in cholestasis-induced organ injury. Apoptosis-inducing factor (AIF) is a flavoprotein located in the inner mitochondrial membrane. This molecule is involved in a distinct pathway of cell death. The current study aimed to evaluate the role of AIF in the pathophysiology of cholestasis-associated hepatic and renal injury. Bile duct ligation (BDL) was used as an animal model of cholestasis. Serum, urine, and tissue samples were collected at scheduled time intervals (3, 7, 14, and 28 days after BDL surgery). Tissues' AIF mRNA levels, as well as serum, urine, and tissue activity of AIF, were measured. Moreover, markers of DNA fragmentation and apoptosis were assessed in the liver and kidney of cholestatic animals. A significant increase in liver and kidney AIF mRNA levels, in addition to increased AIF activity in the liver, kidney, serum, and urine, was detected in BDL rats. DNA fragmentation and apoptosis were raised in the liver and kidney of cholestatic animals, especially at the early stage of the disease. The apoptotic mode of cell death in the liver and kidney was connected to a higher AIF level. These data mention the importance of AIF in the pathogenesis of cholestasis-induced organ injury, especially at the early stage of this disease. Mitochondrial release of apoptosis-inducing factor (AIF) seems to play a pathogenic role in cholestasis-associated hepatic and renal injury. AIF release is directly connected to oxidative stress and mitochondrial impairment in cholestatic animals.

https://link.springer.com/content/pdf/10.1007/s00210-020-02041-7.pdf

Rasool Taghavi

Papers

Agmatine alleviates hepatic and renal injury in a rat model of obstructive jaundice