Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function

Ommati, Mohammad Mehdi; Mohammadi, Hamidreza; Mousavi, Khadijeh; Azarpira, Negar; Farshad, Omid; Dehghani, Reza; Najibi, Asma; Kamran, Sedigheh; Niknahad, Hossein; Heidari, Reza

doi:10.1016/j.livres.2020.12.001

Cited by 23 publications

(11 citation statements)

References 74 publications

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“…The ferric reducing antioxidant power (FRAP) test was applied to measure renal total antioxidant capacity in cholestatic rats [ 15 , 57 ]. Briefly, the FRAP working reagent was freshly prepared by mixing 25 ml of 300 mM acetate buffer (pH = 3.6) with 2.5 ml of 10 mM TPTZ (dissolved in HCl 1N) and 2.5 ml of ferric chloride (FeCl 3 .6H 2 O, 20 mM).…”

Section: Methodsmentioning

confidence: 99%

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Ommati¹,

Hojatnezhad²,

Abdoli³

et al. 2021

ceh

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Aim of the study Cholestasis is the stoppage of bile flow that primarily affects liver function. On the other hand, kidneys are also severely influenced during cholestasis. Cholestasis-induced kidney injury is known as cholemic nephropathy (CN). There is no precise pharmacological option in CN. Previous studies revealed that oxidative stress plays a crucial role in the pathogenesis of CN. On the other hand, the positive effects of pentoxifylline (PTX) against renal injury with different etiologies have been frequently reported. In the current study, the potential nephroprotective role of PTX in cholestasis-induced renal injury is investigated. Material and methods Bile duct ligated (BDL) rats were treated with PTX (10, 50, and 100 mg/kg), and renal markers of oxidative stress, urine level of inflammatory cytokines, as well as renal histopathological alterations were monitored. Results Significant changes in oxidative stress markers were detected in the BDL group. On the other hand, it was found that PTX (10, 50, and 100 mg/kg) significantly ameliorated cholestasis-induced oxidative stress in renal tissue. Renal histopathological changes, including interstitial inflammation, tubular atrophy, fibrosis, and cast formation, were detected in the BDL rats. Moreover, urine pro-inflammatory cytokines [interleukin (IL)-1, IL-9, IL-18, tumor necrosis factor α (TNF-α), and interferon γ (INF-γ)] were significantly increased in the cholestatic animals. PTX (10, 50, and 100 mg/kg, 14 days) significantly ameliorated renal histopathological alterations and urine levels of inflammatory cytokines. Conclusions These data indicate a potential nephroprotective role for PTX in cholestasis. The effects of PTX on oxidative stress parameters and the inflammatory response could play a primary role in its renoprotective mechanisms.

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Section: Methodsmentioning

confidence: 99%

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Ommati¹,

Hojatnezhad²,

Abdoli³

et al. 2021

ceh

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“…Mechanistically, oxidative stress and its related events seem to play a fundamental role in the pathogenesis of cholemic nephropathy and hepatorenal syndrome [38,71,90,186,187]. Additionally, several investigations have revealed the importance of mitochondrial impairment in the mechanism of cholestasis-induced renal injury [60,188]. Mitochondrial impairment in the kidney could lead to an energy crisis and subsequent impairment of high energy demand processes such as reabsorption of chemicals in the renal tubules [189,190].…”

Section: Taurine Depletion In Cholestasis/cirrhosismentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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

Najibi¹,

Rezaei²,

Manthari³

et al. 2022

ceh

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Taurine (TAU) is a free amino acid abundant in the human body. Various physiological roles have been attributed to TAU. At the subcellular level, mitochondria are the primary targets for TAU function. Meanwhile, it has been found that TAU depletion is associated with severe pathologies. Cholestasis is a severe clinical complication that can progress to liver fibrosis, cirrhosis, and hepatic failure. Bile duct ligation (BDL) is a reliable model for assessing cholestasis/cirrhosis and related complications. The current study was designed to investigate the effects of cholestasis/cirrhosis on tissue and mitochondrial TAU reservoirs. Cholestatic rats were monitored (14 and 42 days after BDL surgery), and TAU levels were assessed in various tissues and isolated mitochondria. There was a significant decrease in TAU in the brain, heart, liver, kidney, skeletal muscle, intestine, lung, testis, and ovary of the BDL animals (14 and 42 days after surgery). Mitochondrial levels of TAU were also significantly depleted in BDL animals. Tissue and mitochondrial TAU levels in cirrhotic animals (42 days after the BDL operation) were substantially lower than those in the cholestatic rats (14 days after BDL surgery). These data indicate an essential role for tissue and mitochondrial TAU in preventing organ injury induced by cholestasis/cirrhosis and could justify TAU supplementation for therapeutic purposes.

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“…Testicular and sperm ROS levels were m determined using the fluorescent probe dichlorofluorescein diacetate (DCFH-DA). [64][65][66][67] Briefly, 10 μl of DCFH-DA was added (10 μM final concentration) to sperm (10 6 ) and homogenized testicular samples (1 mg protein/ml). Samples were incubated for 30 min at 35 C in the dark.…”

Section: Testicular and Sperm Reactive Oxygen Speciesmentioning

confidence: 99%

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

Ommati

Ahmadi

Sabouri

et al. 2022

Environmental Toxicology

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Lead (Pb) is a highly toxic heavy metal widely dispersed in the environment because of human industrial activities. Many studies revealed that Pb could adversely affect several organs, including the male reproductive system. Pb‐induced reproductive toxicity could lead to infertility. Thus, finding safe and clinically applicable protective agents against this complication is important. It has been found that oxidative stress plays a fundamental role in the pathogenesis of Pb‐induced reprotoxicity. Glycine is the simplest amino acid with a wide range of pharmacological activities. It has been found that glycine could attenuate oxidative stress and mitochondrial impairment in various experimental models. The current study was designed to evaluate the role of glycine in Pb‐induced reproductive toxicity in male mice. Male BALB/c mice received Pb (20 mg/kg/day; gavage; 35 consecutive days) and treated with glycine (250 and 500 mg/kg/day; gavage; 35 consecutive days). Then, reproductive system weight indices, biomarkers of oxidative stress in the testis and isolated sperm, sperm kinetic, sperm mitochondrial indices, and testis histopathological alterations were monitored. A significant change in testis, epididymis, and Vas deferens weight was evident in Pb‐treated animals. Markers of oxidative stress were also significantly increased in the testis and isolated sperm of the Pb‐treated group. A significant disruption in sperm kinetic was also evident when mice received Pb. Moreover, Pb exposure caused significant deterioration in sperm mitochondrial indices. Tubular injury, tubular desquamation, and decreased spermatogenic index were histopathological alterations detected in Pb‐treated mice. It was found that glycine significantly blunted oxidative stress markers in testis and sperm, improved sperm mitochondrial parameters, causing considerable higher velocity‐related indices (VSL, VCL, and VAP) and percentages of progressively motile sperm, and decreased testis histopathological changes in Pb‐exposed animals. These data suggest glycine as a potential protective agent against Pb‐induced reproductive toxicity. The effects of glycine on oxidative stress markers and mitochondrial function play a key role in its protective mechanism.

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Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function

Cited by 23 publications

References 74 publications

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

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

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

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