Quinacrine Attenuates Cyclosporine-Induced Nephrotoxicity in Rats1

Khader, Abdullah Al; Sulaiman, Mohammed Al; Kishore, Puli Nanda; Morais, Christudas; Tariq, Mohammad

doi:10.1097/00007890-199608270-00001

Cited by 31 publications

(18 citation statements)

References 49 publications

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“…Reduced glutathione, together with GPx, is important in maintaining the structure of mitochondrial and cell membranes. Reductions in GPx activity noted in the CsA treated rats in the present study are consistent with results obtained by others [3]. Flavonoids usually contain one or more aromatic hydroxyl groups in their moiety, which is responsible for their antioxidant activity [58].…”

Section: Discussionsupporting

confidence: 93%

Therapeutic efficacy of naringin on cyclosporine (A) induced nephrotoxicity in rats: Involvement of hemeoxygenase-1

Chandramohan

Parameswari

2013

Pharmacological Reports

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Abstract:Background: Clinically, chronic nephrotoxicity may lead to renal functional impairment and progress to end stage renal failure. The renoprotective effect of a flavonoid naringin (NG) against cyclosporine A (CsA)-induced nephrotoxicity was investigated in this study. Methods: Nephrotoxicity was induced in male albino Wistar rats by injecting 25 mg/kg body weight of CsA for a period of 21 days. CsA-induced rats were also cotreated with 40 mg of NG/kg body weight, orally. Results: After the experimental period, the levels of lipid peroxides (TBARS) and hydroxyl radical (OH ) were found to be elevated, whereas the levels of SOD, catalase, glutathione, vitamin C, E and A were decreased in CsA-induced rats. NG co-treatment significantly decreased the levels of lipid peroxides and hydroxyl radicals and restored the levels of enzymic and non-enzymic antioxidants in renal tissues. Histological analysis revealed that CsA administration caused severe and widespread necrosis with dilatation of proximal tubules, vacuolization, tubular cell desquamation and intraluminal cast formation with massive infiltration of inflammatory cells. CsA-induced histopathological renal changes were minimal in animals which received NG treatment. The western blot and confocal microscopic expression of heme oxygenase-1 was restored by NG. In CsA-induced animals the expression was reduced compared to NG treated animals. Conclusions: The present study reveals that NG can act as effective renoprotective drug against CsA-induced toxicity.

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Section: Discussionsupporting

confidence: 93%

Therapeutic efficacy of naringin on cyclosporine (A) induced nephrotoxicity in rats: Involvement of hemeoxygenase-1

Chandramohan

Parameswari

2013

Pharmacological Reports

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“…The depletion of GSH stores and a reduction in GPX activity in the kidney obtained in the present study are consistent with other previous investigations. 32,49 Depletion of renal GSH stores by CsA in the present study could account for the inhibition of renal GPX activity. Vaziri et al 50 have induced hypertension in normal rats by glutathione depletion.…”

Section: Discussionmentioning

confidence: 57%

Taurine Attenuates Hypertension and Renal Dysfunction Induced by Cyclosporine a in Rats

Hagar¹,

Etter²,

Arafa

2006

Clin Exp Pharma Physio

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Cyclosporine A (CsA) is the first-line immunosuppressant used for the management of solid organ transplantation and autoimmune diseases. Nephrotoxicity is the major limitation of CsA use. Recent evidence suggests that reactive oxygen species (ROS) play an important role in mediating CsA-induced hypertension and nephrotoxicity. Taurine, the major intracellular free beta-amino acid, is known to be an endogenous anti-oxidant and membrane-stabilizing agent. The present study was designed to investigate the effects of taurine on CsA-induced oxidative stress, hypertension and renal dysfunction. 2. Animals were assigned into four groups of seven rats each as follows: (i) control group, receiving vehicle (olive oil; 1 mL/kg, s.c.); (ii) CsA group, given CsA (25 mg/kg per day, s.c.) for 21 days; (iii) taurine group, supplemented with taurine (1% in the drinking water); and (iv) taurine + CsA group, treated with taurine 3 days before and concurrently during CsA injections for 21 days. 3. Cyclosporine A administration elevated blood pressure, reduced serum nitric oxide (NO) levels and deteriorated renal function, as assessed by increased serum creatinine levels and proteinuria and reduced urine flow rate and creatinine clearance compared with vehicle-treated rats. Cyclosporine A induced oxidative stress, as indicated by increased renal tissue concentrations of thiobarbituric acid-reactive substances and reduced concentrations of renal glutathione, glutathione peroxidase and superoxide dismutase. Conversely, no change was noted in renal catalase activity. Moreover, the kidneys of CsA-treated rats showed interstitial inflammation and renal tubular atrophy. 4. Taurine markedly reduced elevated blood pressure, attenuated renal dysfunction and the reduction in serum NO levels and counteracted the deleterious effects of CsA on oxidative stress markers. Furthermore, taurine ameliorated CsA-induced morphological changes. 5. These data clearly indicate the protective potential of taurine against CsA-induced hypertension and nephrotoxicity and suggest a significant contribution of its anti-oxidant property to this beneficial effect.

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“…Some workers, however, report that the tubular vacuolization in patients clinically classified as cyclosporine toxicity is similar to that described in acute tubular necrosis (65). Likewise other studies show no differences in the spectrum of tubular changes in renal transplant patients treated with either cyclosporine or azathioprine (66,67) Experimental models of tacrolimus and cyclosporine toxicity with nonisometric tubular vacuolation also are described in the literature (68,69) We commonly find isometric tubular vacuolization in biopsies with significant rejection and have wondered whether this might be the result of immunologically mediated injury in this setting. It is also possible to argue that these cases are examples of concurrent rejection and toxicity (25) From a practical standpoint, it is safe to use tubular vacuolization as flag indicating the need to lower the dose of tacrolimus or cyclosporine, provided the biopsy shows no change of rejection.…”

Section: Tubular Vacuolizationmentioning

confidence: 87%