Cytoprotective Properties of Carnosine against Isoniazid-Induced Toxicity in Primary Cultured Rat Hepatocytes

Eftekhari, Aziz; Heidari, Reza; Ahmadian, Elham; Eghbal, Mohammad Ali

doi:10.15171/ps.2018.38

Cited by 9 publications

(5 citation statements)

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“…76 CAR also significantly decreased mitochondrial impairment and enhanced cellular energy metabolism. 84,85 In the current study, we found that CAR Pharmaceutical Sciences, 2021, 27(1), 32-45 | 40 treatment significantly diminished oxidative stress and cellular macromolecules injury in the kidney of cholestatic animals. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a fundamental signaling pathway for increasing the cellular antioxidant defense in oxidative stress.…”

Section: Figuresupporting

confidence: 50%

Carnosine Mitigates Biomarkers of Oxidative Stress, Improves Mitochondrial Function, and Alleviates Histopathological Alterations in the Renal Tissue of Cholestatic Rats

et al. 2020

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Background: Cholestatic liver disease primarily affects hepatic tissue. Cholestasis could also influence the function of other organs rather than the liver. Cholestasis-induced kidney injury is a severe clinical complication known as "cholemic nephropathy" (CN). Bile duct ligation (BDL) is a trustworthy experimental model for inducing CN. Although the precise mechanism of renal injury in cholestasis is not fully recognized, several studies revealed the role of oxidative stress in CN. There is no promising pharmacological intervention against CN. Carnosine (CAR) is a peptide extensively investigated for its pharmacological effects. Radical scavenging and antioxidative stress are major features of CAR. The current study aimed to evaluate the role of CAR supplementation on the CN. Methods: CAR was administered (250 and 500 mg/kg, i.p) to BDL rats for 14 consecutive days. Urine and serum markers of renal injury, biomarkers of oxidative stress in the kidney tissue, and renal histopathological alterations were monitored. Results: Significant elevation in oxidative stress biomarkers, including ROS formation, lipid peroxidation, oxidized glutathione (GSSG) levels, and protein carbonylation were found in the kidney of BDL rats. Moreover, renal tissue antioxidant capacity and reduced glutathione (GSH) levels were significantly decreased in the organ of cholestatic animals. Renal histopathological changes, including tubular atrophy, interstitial inflammation, tissue fibrosis, and cast formation, were detected in the kidney of BDL rats. It was found that CAR administration significantly protected the kidney of cholestatic animals. Conclusion: The antioxidative properties of this peptide might play a fundamental role in its protective properties during cholestasis.

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Section: Figuresupporting

confidence: 50%

Carnosine Mitigates Biomarkers of Oxidative Stress, Improves Mitochondrial Function, and Alleviates Histopathological Alterations in the Renal Tissue of Cholestatic Rats

et al. 2020

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“…Fatty acid metabolism was reported to be in uenced by Vitamin D de ciency and consequently increased the risk of tuberculosis infection [31]. N-Acetylgalactosamine, a substrate of arylsulfatase B (N-acetylgalactosamine-4-sulfatase), was proved to contribute to intracellular oxygen signaling and in uence hypoxia [32], mannitol, an inhibitor of CYP2E1 [33], could improve lung function in cystic brosis [34], Deoxyuridine troposphere nucleotidohydrolase, using deoxyuridine as a substrate, is a drug target against mycobacterium infections [35], Carnosine is an endogenous antioxidant widely distributed in excitable tissues[36], owning cytoprotective properties in primary cultured rat hepatocytes [37], Methylguanidine could inhibit lymphocyte transformation in vitro [38]. The concordance between the ndings in previous reports and the present study suggested that the M. marinum challenged zebra sh is a suitable model in mimicking tuberculosis infection in human.…”

Section: Discussionmentioning

confidence: 99%

Calcitriol Exerts Prophylactic Anti-Mycobacterium Effect In A Dose-Dependent Manner

Gao

et al. 2021

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Vitamin D was empirically applied for Tuberculosis (TB) treatment in the past, and is currently used as an adjuvant for TB therapy. Although an increasing pile of evidences suggests that vitamin D has no therapeutic effect against TB infection, the prophylactic effect of vitamin D in preventing TB remains largely undetermined. To experimentally valuate the potential prophylactic effect of calcitriol (the active form of vitamin D) against mycobacterium infection, we performed dose-gradient calcitriol soaking in 30-day-old zebrafish before Mycobacterium marinum (M. marinum) challenge through tail vein injection. 1H-NMR metabolomics analysis was further performed for illustration of potential mechanisms underlying the prophylactic effect of calcitriol against M. marinum. The results suggested that calcitriol exerts dose-dependent prophylactic anti-mycobacterium effects, i.e., the bacterial load and the corresponding inflammatory factors (IL-1β, TNF-α, and IFN-γ) expressions in M. marinum challenged zebrafish were reduced by low-dose (25 µg/L) or high-dose (2500 µg/L) calcitriol soaking, rather than by moderate-dose (250 µg/L) calcitriol soaking. Body weight of the M. marinum challenged zebrafish was recovered by high-dose prophylactic calcitriol soaking rather than by low-dose or moderate-dose calcitriol. The 1H-NMR metabolomic profiling identified 29 metabolites with altered abundance among the dose-gradient calcitriol groups, among which 22 metabolites were co-varied with the dose of calcitriol, the rest 7 metabolites were co-varied with the bacterial load and the inflammatory response in term of cytokine expression. Further pathway analysis indicated that the glycine, serine, and threonine metabolism pathway was the activated in both of the two metabolite groups, indicating that the pathway was altered by dose-gradient of calcitriol and was in response to M. marinum infection in zebrafish. The results of the present study suggested that the activation of glycine, serine and threonine metabolism pathway may play a potential role for the dose-dependent anti-mycobacterium effect induced by prophylactic calcitriol soaking.

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“…A commercial kit (Pars Azmun ® , Tehran, Iran) and Mindray ® BS-200 autoanalyzer (Guangzhou, China) were used to assess cells lactate dehydrogenase (LDH) levels in cultured LCs ( 95 , 96 ). Isolated LCs were treated with different concentrations of Li + (0, 10, 50, and 100 ppm) after the incubation period.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2021

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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.

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Cytoprotective Properties of Carnosine against Isoniazid-Induced Toxicity in Primary Cultured Rat Hepatocytes

Cited by 9 publications

References 36 publications

Carnosine Mitigates Biomarkers of Oxidative Stress, Improves Mitochondrial Function, and Alleviates Histopathological Alterations in the Renal Tissue of Cholestatic Rats

Carnosine Mitigates Biomarkers of Oxidative Stress, Improves Mitochondrial Function, and Alleviates Histopathological Alterations in the Renal Tissue of Cholestatic Rats

Calcitriol Exerts Prophylactic Anti-Mycobacterium Effect In A Dose-Dependent Manner

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

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