INTEGRATED EVALUATION OF GUT MICROBIOTA ALTERATIONS, ENDOCRINE DYSFUNCTION, AND GENOTOXIC STRESS IN HEPATIC CIRRHOSIS

Abstract

Hepatic cirrhosis, chronic liver disease demonstrates systemic problems associated with oxidative stress, misbalance of hormones, and genotoxicity. This study was aimed at measuring oxidative stress markers, concentrations of hormones and DNA damage, in individuals with hepatic cirrhosis. There were two groups in the study; 30 people with cirrhosis and 30 controls of a similar age and gender, age ranged between 20 and 50. About 5 mL of blood and stool samples were collected from District Peshawar and analyzed in Institute of Molecular Medicine and Alpha Genomic Lab Islamabad. Biological samples were examined using comet assay and the indicators of oxidative stress (MDA, SOD, GSH), and hormones such as progesterone, testosterone, growth hormone, TSH, T3, and T4 were determined. DNA tail length was significantly greater in Cirrhosis patients as compared to controls in the 20–35 age group. Notably, cirrhosis patients showed higher DNA tail length measurements with 20–35 and 35–50 years varying from 24.34 ± 1.78 µm and 30.78 ± 1.52 µm, respectively, as compared to controls varying from 10.75 ± 0.52 µm and 14.11 ± 0.75 µm at 20–35 and 30–50 years respectively. Increase in MDA levels of cirrhosis patients was observed such as:  In age group 20–35 years, MDA levels were 11.40 ± 1.02 Nmol/mL and in age group 35–50 years: it was 12.22 ± 1.06 Nmol/mL in contrast to controls at 8.22 ± 0.58 and 7.46 ± 0.59 Nmol/mL. Patients showed increased concentrations of SOD (72.60 ± 1.55 and 80.75 ± 1.29 Nmol/mL) compared to controls at (63.03 ± 1.14 and 65.82 ± 0.95 Nmol/mL). The levels of GSH were significantly lower with cirrhotic individuals (55.46±0.84 and 61.53±0.98 Nmol/mL) than controls (67.12±0.58 and 73.32±0.49 Nmol/mL). Patients with cirrhosis had notably low progesterone and testosterone levels and different TSH readings (decreased in comparison to healthy subjects). Increased T3 and T4 were observed in the present study. The results imply there is cross-talk between genotoxicity, oxidative stress and endocrine disruption in hepatic cirrhosis, which may play a major role in the development of the disease and systemic complications.