Mitochondrial DNA damage and its effect on mitochondrial function in rats with obstructive jaundice

Abstract

This study investigated mitochondrial DNA (mtDNA) damage in rats with obstructive jaundice (OJ) and to explore its effect on mitochondrial and hepatic function. Forty-eight male Wistar rats were randomly divided into two groups: sham-operated (Sham) and bile duct ligation (BDL). Blood and tissue samples were collected from the two groups on days 1, 4, 7 and 14 following surgery. Hepatic and mitochondrial function were measured. Long and accurate PCR, restriction enzyme digestion and gene sequencing were used to analyze the locations of mtDNA deletions. In addition, quantitative fluorescent PCR was used to measure the relative amounts of total DNA in hepatocytes and mtDNA deletions. Results showed that the hepatic and mitochondrial function was compromised in the BDL group compared to the Sham group. Notably, a novel 11,194-bp mtDNA deletion (nucleotide positions 4101-15294) and fewer mtDNA copies were found compared to the Sham group. With prolonged ligation time, there was a decrease in the copy number, while the ratio of mtDNA deletions to total mtDNA levels increased in the BDL group. These changes were consistent with damage to hepatic and mitochondrial function. A novel 11,194-bp mtDNA deletion and fewer mtDNA copies were detected in hepatocytes of rats with OJ. The mtDNA deletions may therefore be an important factor leading to mitochondrial and hepatic dysfunction.