THE IMMUNE AND METABOLIC IMPACTE OF TESTESTERONE ON MICE MODEL OF LIVER FIBROSIS
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Date
2023-06-14
Authors
Hadeel Moneer Snober
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Abstract
Background: Natural killer (NK) cells showed an anti-fibrotic effect; however, their function is thought to be impaired in advanced liver injury. The objective of this study was to evaluate the immune response and metabolic impact of testosterone on mice model of liver injury.
Methods: Carbon-tetrachloride (i.p injected) of acute (2 weeks) and chronic (4 weeks) models of male mice of liver injury was performed. Testosterone (4 mg/kg mouse body weight) was injected intraperitoneal injection following the first week of acute model of CCl4 and following the second week of the chronic model of CCl4. At the end of experiments, mice were sacrificed, and serum were collected for assessing liver enzymes of ALT, AST, inflammatory marker of IL-6, metabolic makers of C-peptide levels as well as for lipid and glucose profiles. Livers were harvested and used for histological assessments for inflammation and for fibrosis. Fibrosis profile from liver extracts; SMA and Collagen III, The samples underwent assessment utilizing the real-time polymerase chain reaction (PCR) technique. Moreover, liver tissue-resident NK cells were isolated and evaluated for their activity through assessing INF- and IL-6 receptor by the ELISA and flow-cytometry respectively.
Results: The serum levels of ALT, AST, and IL-6, as well as metabolic evaluations of cholesterol, triglyceride, C-peptide, fasting blood sugar, and fibrotic profiles, exhibited a linear correlation with the progression of the disease. Histological characterization of the liver was worsened in the chronic model of liver injury. Testosterone-treated mice exhibit a significant reduction in collagen depositions with less dense fibrosis tissue associated with reduced liver injury enzymes and metabolic markers in both the acute and the chronic CCl4 mice model after testosterone treatment (P<0.05). Moreover, testosterone treatments displayed significant decrease in serum IL-6 of 2.4-fold (p=0.0001) and 2.3-fold (p=0.0003) in the acute and chronic models, respectively (p=0.002) and data were associated with increase in INF-release from NK associated with a reduction in their IL-6 receptor expressions (P<0.05).
Conclusion: Testosterone has an anti-inflammatory and anti-fibrotic action by storing histology for lowering SMA and Col III levels as well as decreasing ALT and AST levels. In CCl4-induced mice, testosterone improved the metabolic profile by lowering cholesterol, triglyceride, FBS, and C-peptide levels. Testosterone has an anti-inflammatory impact via decreasing inflammatory cytokine levels (lower IL-6).Testosterone treatment of CCl4-mice restored trNK cell function by increasing NK INF-g and decreasing IL-6 receptor levels. These findings emphasize testosterone's immune-modulatory effects, which are linked to its anti-inflammatory and anti-fibrotic capabilities. Our results suggest an anti-inflammatory and anti-fibrotic treatment approach of testosterone for delaying disease progressions.
Keywords: Liver fibrosis; Mice Model; Testosterone; Immune And Metabolic Impact.