Disturbed mitochondrial redox state and tissue energy charge in cholestasis

Abstract

The liver is the primary organ affected by cholestasis. However, the brain, skeletal muscle, heart, and kidney are also severely influenced by cholestasis/cirrhosis. However, little is known about the molecular mechanisms of organ injury in cholestasis. The current study was designed to evaluate the mitochondrial glutathione redox state as a significant index in cell death. Moreover, tissue energy charge (EC) was calculated. Rats underwent bile duct ligation (BDL) and the brain, heart, liver, kidney, and skeletal muscle mitochondria were assessed at scheduled time intervals (3, 7, 14, and 28 days after BDL). A significant decrease in mitochondrial glutathione redox state and EC was detected in BDL animals. Moreover, disturbed mitochondrial indices were evident in different organs of BDL rats. These data could offer new insight into the mechanisms of organ injury and the source of oxidative stress during cholestasis and might provide novel therapeutic strategies against these complications.

Glycine protects the male reproductive system against lead toxicity via alleviating oxidative stress, preventing sperm mitochondrial impairment, improving kinematics of sperm, and blunting the downregulation of enzymes involved in the steroidogenesis

“…Then, 100 μl of KOH (3 M) was added, and samples were centrifuged. As previously described, the ATP levels were analyzed using a reverse‐phase C‐18 column (10 mm, μBondapak®, Waters, Ireland) 63 . The mobile phase consisted of KH 2 PO 4 buffer (100 mM, pH = 6).…”

“…The mobile phase consisted of KH 2 PO 4 buffer (100 mM, pH = 6). The UV detector was set at λ = 254 nm 63 …”

“…As previously described, the ATP levels were analyzed using a reverse-phase C-18 column (10 mm, μBondapak ® , Waters, Ireland). 63 The mobile phase consisted of KH 2 PO 4 buffer (100 mM, pH = 6). The UV detector was set at λ = 254 nm.…”

Cellular and mitochondrial taurine depletion in bile duct ligated rats: a justification for taurine supplementation in cholestasis/cirrhosis

“…Tissue samples including brain, heart, liver, kidney, skeletal muscle, lung, intestine, ovary, testis, and blood samples were collected. Equal amounts of tissue samples (5% w : v) were homogenized in a solution containing 70 mM mannitol, 220 mM sucrose, 2 mM HEPES, 0.5 mM EGTA, and 0.1% essentially fatty acid-free bovine serum albumin (pH = 7.4) [63]. One milliliter of each blood sample was centrifuged (4000 g, 15 min, 4°C) and used for serum biochemical analysis.…”

“…Severe liver histopathological changes, cardiac dysfunction, skeletal muscle atrophy, muscle mass loss (sarcopenia), brain and lung injury, hepatic encephalopathy, intestinal and renal damage (cholemic nephropathy), and poor reproductive organs function are appropriately induced in the BDL model of cholestasis [33,36,[42][43][44][45][46][47]. On the other hand, various investigations, including our research on BDL animals, indicate the essential role of mitochondrial impairment in the pathogenesis of cholestasis-associated complications [23,33,38,41,[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66].…”