The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

Taurine (2-aminoethane sulfonic acid) is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid) is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 µM, 100 µM and 1000 µM) of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5‑Fluorouracil, Doxorubicin and Dacarbazine) via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+). Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione) were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug‑treated livers. It was found that taurine (5 and 10 mM) and glycine (5 and 10 mM) administration significantly mitigated the biomarkers of liver injury and attenuated drug‑induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.</p

Investigation of the effects of mechanical and underfloor heating systems on the COVID-19 viruses distribution

Investigation of the spread of pollutants and especially pathogenic particles in the interior of today's buildings has become an integral part of the design of such buildings. When the Coronavirus is prevalent in the world, it is necessary to pay attention to the spread of the virus in the interior of residential apartments. In the present study, the Coronavirus particles emitted from the sneezing of a sick person in the bedroom of a residential apartment were tracked. Meanwhile, the degree of exposure of a mannequin that has been placed in the living room playing the role of a healthy person is examined. In this research, a segregated solution of steady-state flow and an unsteady particle solution have been separately used: a suitable, accurate, and optimal solution in particle studies. A comparison of the results shows that underfloor heating creates a healthier space around the healthy person's respiratory system, but instead, we will see more polluted areas around the sick person. According to the PRE results, the PRE value for a mechanical heating system is higher than a floor heating system. Therefore, it is recommended to use mechanical heating system in the apartments where the person with COVID-19 is hospitalized

Sulfasalazine-induced renal and hepatic injury in rats and the protective role of taurine

Introduction: Sulfasalazine is a drug commonly administrated against inflammatory-based disorders. On the other hand, kidney and liver injury are serious adverse events accompanied by sulfasalazine administration. No specific therapeutic option is available against this complication. The current investigation was designed to evaluate the potential protective effects of taurine against sulfasalazine-induced kidney and liver injury in rats. Methods: Male Sprague-Dawley rats were administered with sulfasalazine (600 mg/kg, oral) for 14 consecutive days. Animals received different doses of taurine (250, 500 and 1000 mg/kg, i.p.) every day. Markers of organ injury were evaluated on day 15th, 24 h after the last dose of sulfasalazine. Results: Sulfasalazine caused renal and hepatic injury as judged by an increase in serum level of creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP). The levels of reactive oxygen species (ROS) and lipid peroxidation were raised in kidney and liver of sulfasalazine-treated animals. Moreover, tissue glutathione reservoirs were depleted after sulfasalazine administration. Histopathological changes of kidney and liver also endorsed organ injury. Taurine administration (250, 500 and 1000 mg/kg/day, i.p) alleviated sulfasalazine-induced renal and hepatic damage. Conclusion: Taurine administration could serve as a potential protective agent with therapeutic capabilities against sulfasalazine adverse effects

Evaluation of Oxidative Stress in Combination Therapy with D-penicillamine and N-Acetylcysteine (NAC) in Lead Poisoning in Opium Addicts

Background: N-acetylcysteine (NAC) is a putative antioxidant and has gained attention as a promising agent for chelating heavy metals including lead. Considering the animal studies results, we hypothesized that adding NAC to the treatment regimen may improve the success of treatment with lead chelators. Methods: A total of 46 patients who were lead-poisoned opioid addicts were divided into two groups randomly and treated with d-penicillamine (DP, 1g/day in four equal divided doses) and NAC+DP (1 g/day + 150 mg/kg/day). The efficacy of treatment was evaluated by hospitalization period. Meanwhile, the oxidative stress parameters including lipid peroxidation, protein carbonyl, total antioxidant capacity (TAC), glutathione concentration and super oxide dismutase (SOD) activity were determined on admission and discharge and compared with healthy normal controls. Results: Hospitalization period was not different between the two groups. Treatment with DP and DP+NAC significantly decreased oxidative stress in patients. On the discharge day, the SOD activity and TAC were significantly higher in DP+NAC group in comparison with the DP group. Conclusion: Although NAC recovers antioxidant capacity, the advantages of NAC in improvement of DP efficacy in lead poisoning is questionable. Further studies with larger sample size and combination with other chelators are recommended

Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats

Purpose: Accumulating evidence suggests that drug exposure during a modest inflammation induced by bacterial lipopolysaccharide (LPS) might increase the risk of drug-induced liver injury. The current investigation was designed to test if antimalarial drugs hepatotoxicity is augmented in LPS‑treated animals. Methods: Rats were pre-treated with LPS (100 µg/kg, i.p). Afterward, non-hepatotoxic doses of amodiaquine (25, 50 and 100 mg/kg, oral) and chloroquine (25, 50 and 100 mg/kg, oral) were administered. Results: Interestingly, liver injury was evident only in animals treated with both drug and LPS as estimated by pathological changes in serum biochemistry (ALT, AST, LDH, and TNF-α), and liver tissue (severe hepatitis, endotheliitis, and sinusoidal congestion). An increase in liver myeloperoxidase enzyme activity, lipid peroxidation, and protein carbonylation, along with tissue glutathione depletion were also detected in LPS and drug co-treated animals. Conclusion: Antimalarial drugs rendered hepatotoxic in animals undergoing a modest inflammation. These results indicate a synergistic liver injury from co-exposure to antimalarial drugs and inflammation

The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

Taurine (2-aminoethane sulfonic acid) is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid) is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 μM, 100 μM and 1000 μM) of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5 Fluorouracil, Doxorubicin and Dacarbazine) via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+). Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione) were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug treated livers. It was found that taurine (5 and 10 mM) and glycine (5 and 10 mM) administration significantly mitigated the biomarkers of liver injury and attenuated drug induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury

Antimalarial Drugs-Induced Hepatic Injury in Rats and the Protective Role of Carnosine

Background: Chloroquine and amodiaquine are used in the prophylaxis and treatment of malaria. However, hepatic injury is associated with malaria drug therapy. On the other hand, there is no promising hepatoprotective agent for prophylaxis or treatment of antimalarial drugs‑induced liver injury. Carnosine is a naturally occurring peptide with pleiotropic protective properties in different tissues. This investigation aimed to evaluate the effect of carnosine administration in antimalarial drugs-induced hepatic injury in rats. Methods: Animals were treated with amodiaquine (180 mg/kg, oral) or chloroquine (970 mg/kg, oral). Carnosine (250, 500 and 1000 mg/kg, i.p) was administered as the hepatoprotective agent against antimalarial drugs liver injury. Results: Liver injury was manifested biochemically by a significant increase in serum level of ALT, LDH, and AST. In addition, hepatic tissue from antimalarial drugs‐treated rats showed a significant increase in reactive oxygen species (ROS), lipid peroxidation and protein carbonylation along with a decrease in hepatic glutathione reservoirs and total antioxidant capacity. Moreover, the liver histopathologic evaluation revealed significant congestion, inflammation, and necrosis in amodiaquine and/or chloroquine-treated animals. Carnosine administration significantly alleviated antimalarial drugs-induced pathologic changes in serum biochemistry and liver tissue. Conclusion: Our data suggest that carnosine possesses protective properties against amodiaquine and/or chloroquine‑induced liver injury possibly through mitigation of drug-induced oxidative stress and its consequent events

Effect of taurine on chronic and acute liver injury: Focus on blood and brain ammonia

Hyperammonemia is associated with chronic and acute liver injury. There is no promising therapeutic agent against ammonia-induced complications. Hence, finding therapeutic molecules with safe profile of administration has clinical value. The present study was conducted to evaluate the role of taurine (TA) administration on plasma and brain ammonia and its consequent events in different models of chronic and acute liver injury and hyperammonemia. Bile duct ligated (BDL) rats were used as a model of chronic liver injury. Thioacetamide and acetaminophen-induced acute liver failure were used as acute liver injury models. A high level of ammonia was detected in blood and brain of experimental groups. An increase in brain ammonia level coincided with a decreased total locomotor activity of animals and significant changes in the biochemistry of blood and also liver tissue. TA administration (500 and 1000 mg/kg, i.p), effectively alleviated liver injury and its consequent events including rise in plasma and brain ammonia and brain edema. The data suggested that TA is not only a useful and safe agent to preserve liver function, but also prevented hyperammonemia as a deleterious consequence of acute and chronic liver injury. Keywords: Amino acid, Ammonia, Brain edema, Hepatic encephalopathy, Hepatic injury, Hepatoprotectiv