Metformin Attenuates Cyclosporine A-induced Renal Fibrosis in Rats

The use of cyclosporine A (CsA) as an immunosuppressive agent is often limited owing to its hepatotoxic and nephrotoxic properties. The present study was designed to evaluate the protective effect of metformin and silymarin in a rat model of CsA induced hepatorenal toxicity. The study included seven groups of Wistar albino rats (n = 6 per group): normal control, experimental control (CsA alone, 25 mg/kg), CsA + metformin (50 and 500 mg/kg), CsA + silymarin (50 and 200 mg/kg) and CsA + vitamin E (100 mg/kg). All the drugs were given daily for a period of 21 days by oral gavage and their effect was evaluated on serum levels of organ function markers (serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, bilirubin, urea/blood urea nitrogen, creatinine), markers of oxidative stress (thiobarbituric acid reactive substances, glutathione, superoxide dismutase), inflammation (nitrite, myeloperoxidase, tumour necrosis factor‐alpha, prostaglandin E2), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling positivity) in addition to tissue histology, cyclooxygenase (COX)‐2 and inducible nitric oxide synthase (iNOS) immunoreactivity. Administration of metformin and silymarin along with CsA ameliorated functional damage to liver and kidneys in a dose‐dependent manner. Significant and comparable improvement in the tissue levels of oxidative stress, inflammation, apoptotic markers was also observed following treatment with both the test drugs. Normalization of histology scores, as well as COX‐2 and iNOS immunoreactivity scores, further strengthened these findings. The hepatoprotective and nephroprotective effects of metformin and silymarin were comparable and matched with that of reference drug, vitamin E. The findings of the present study suggest that both metformin and silymarin have a potential for clinical use in patients receiving long‐term CsA treatment to maintain their liver and kidney functions.

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“…Besides, a reduction in the serum levels of organ function markers was also observed with all the three drugs. [ 27,30,47–50 ]…”

Section: Discussionmentioning

confidence: 99%

“…[ 17,18,28,54 ] A recent study has also shown that metformin exerts its nephroprotective action by attenuating renal fibrotic changes induced by chronic CsA administration. [ 50 ]…”

Section: Discussionmentioning

confidence: 99%

Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation

Vangaveti

Das

Kumar

2020

J Biochem & Molecular Tox

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“…Additionally, metformin treatment has been demonstrated to slow cystogenesis in a murine model of autosomal-dominant polycystic kidney disease [ 30 ]. It has also been reported to reduce renal fibrosis in high-fat diet-fed rats [ 31 ], unilateral ureteral obstruction (UUO) mice [ 32 , 33 ], folic acid-induced renal fibrosis [ 32 , 34 ], adenine-induced chronic kidney disease rats [ 35 ], and cyclosporine A-induced renal fibrosis rats [ 36 ]. Moreover, accumulating evidence has shown that metformin has great potential in alleviating the progression of fibrosis in various organs.…”

Section: Experimental and Clinical Evidence Of The Antifibrotic Effects Of Metforminmentioning

confidence: 99%

Metformin and Fibrosis: A Review of Existing Evidence and Mechanisms

Liu

et al. 2021

Journal of Diabetes Research

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Fibrosis is a physiological response to organ injury and is characterized by the excessive deposition of connective tissue components in an organ, which results in the disruption of physiological architecture and organ remodeling, ultimately leading to organ failure and death. Fibrosis in the lung, kidney, and liver accounts for a substantial proportion of the global burden of disability and mortality. To date, there are no effective therapeutic strategies for controlling fibrosis. A class of metabolically targeted chemicals, such as adenosine monophosphate-activated protein kinase (AMPK) activators and peroxisome proliferator-activated receptor (PPAR) agonists, shows strong potential in fighting fibrosis. Metformin, which is a potent AMPK activator and is the only recommended first-line drug for the treatment of type 2 diabetes, has emerged as a promising method of fibrosis reduction or reversion. In this review, we first summarize the key experimental and clinical studies that have specifically investigated the effects of metformin on organ fibrosis. Then, we discuss the mechanisms involved in mediating the antifibrotic effects of metformin in depth.

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“…As a commonly used clinical immunosuppressant, cyclosporine A (CsA) has been widely prescribed for inhibiting rejection after organ transplantation. Many experimental studies showed that long-term use of CsA could contribute to progressive renal interstitial fibrosis, renal cell apoptosis, and immune cell infiltration ( Wu et al, 2018 ; Lin et al, 2019 ). Findings from Doh’s group showed that Panax ginseng C.A.Mey.…”

Section: Role Of Panax Ginseng Camey In Different Nephropathymentioning

confidence: 99%

Panax Ginseng C.A.Mey. as Medicine: The Potential Use of Panax Ginseng C.A.Mey. as a Remedy for Kidney Protection from a Pharmacological Perspective

Jin

Zhang

et al. 2021

Front. Pharmacol.

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Panax ginseng C.A.Mey. has been widely consumed as food/diet supplements from natural sources, and its therapeutic properties have also aroused widespread concern. Therapeutic properties of Panax ginseng C.A.Mey. such as anti-inflammatory, ameliorating chronic inflammation, enhancing the immunity, resisting the oxidation again, and regulating the glucose and lipid metabolism have been widely reported. Recent years, lots of interesting studies have reported the potential use of Panax ginseng C.A.Mey. in the management of DKD. DKD has become the leading cause of end-stage renal disease worldwide, which increases the risk of premature death and poses a serious financial burden. Although DKD is somehow controllable with different drugs such as Angiotensin-Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor Blockers (ARB) and lowering-glucose agents, modern dietary changes associated with DKD have facilitated research to assess the preventive and therapeutic merits of diet supplements from natural sources as medicine including Panax ginseng C.A.Mey. Findings from many scientific evidences have suggested that Panax ginseng C.A.Mey. can relieve the pathological status in cellular and animal models of DKD. Moreover, a few studies showed that alleviation of clinical phenotype such as reducing albuminuria, serum creatinine and renal anemia in DKD patients after application or consumption of Panax ginseng C.A.Mey.. Therefore, this review aims to discuss the effectiveness of Panax ginseng C.A.Mey. as medicine for targeting pathological phenotypes in DKD from a pharmacological perspective. This review will provide new insights into the potential understanding use of Panax ginseng C.A.Mey. in the management of DKD in clinical settings.

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Metformin Attenuates Cyclosporine A-induced Renal Fibrosis in Rats

Cited by 22 publications

References 51 publications

Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation

Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation

Metformin and Fibrosis: A Review of Existing Evidence and Mechanisms

Panax Ginseng C.A.Mey. as Medicine: The Potential Use of Panax Ginseng C.A.Mey. as a Remedy for Kidney Protection from a Pharmacological Perspective

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