Is there any way to protect from tacrolimus-induced renal and pancreas injury?

BACKGROUND: The aim of this study was to explore effects of erythropoietin and pentoxifylline in tacrolimus-induced pancreatic beta cell and renal injury in rats. METHODS: Rats in group I were given saline; rats in group II were injected with tacrolimus; rats in group III were received erythropoietin (Epo) and tacrolimus; while rats in group IV were injected pentoxifylline (Ptx) plus tacrolimus for nine d. On 10th day, blood and tissue samples were taken for biochemical and pathological evaluations. RESULTS: Tacrolimus-injected animals exhibited significant elevation in blood urea nitrogen (BUN), and serum BUN levels were improved in rats pretreated with Ptx. Significantly more apoptotic nuclei were observed in kidneys of tacrolimus group. In rats subjected to tacrolimus and pretreated with Epo, there was significant decrease in apoptotic nuclei staining than those in tacrolimus group. Blood trough levels of tacrolimus were significantly higher in erythropoietin-pretreated group, although same amount of tacrolimus was injected with other groups. CONCLUSION: Results of our study demonstrated significant antiapoptotic effects of erythropoietin on renal tubules, increasing effect of erythropoietin on tacrolimus blood levels, and insignificant antioxidant effects of both erythropoietin and pentoxifylline on renal and pancreas tissues. Study with clinically greater tacrolimus levels may be useful to confirm these findings.

Protective effect of the grape seed proanthocyanidin extract in a rat model of contrast-induced nephropathy.

AIM: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute renal failure. Although it is so common, there has been no approved therapy yet. We aimed to investigate the effect of grape seed proanthocyanidin extract (GSPE) on preventing CIN. MATERIALS AND METHODS: 24 rats were divided into four groups as control group, GSPE group, contrast medium (CM) group, and CM+GSPE group. The experiment was discontinued on the ninth day. Blood samples were obtained for the measurement of renal function parameters. Renal tissues of the rats were removed for the analysis of oxidative system parameters. In addition to renal histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. RESULTS: There was a significant increase in BUN, creatinine, malondialdehyde (MDA) levels, apoptotic index (AI) and histopathological alteration in the CM group as compared to the control group. Furthermore, BUN, creatinine, MDA, total oxidant system and oxidative stress index levels, AI as well as renal histopathological alteration were significantly decreased in the CM+GSPE group. CONCLUSION: For the first time in the literature, we showed that GSPE provided biochemical and histopathological improvement in CIN. Our findings revealed that this improvement was associated with the decrease in oxidative damage and apoptosis.

Anti-apoptotic and anti-oxidant effects of grape seed proanthocyanidin extract in preventing cyclosporine A-induced nephropathy.

AIM: Although the pathogenesis of cyclosporine (CsA) nephropathy is not completely understood, it is attributed to oxidative damage and apoptosis. Grape seed proanthocyanidin extract (GSPE) is a molecule with anti-oxidant and anti-apoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing CsA nephropathy. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups. The control, GSPE, CsA and CsA+GSPE groups were given 1 mL olive oil, 100 mg/kg GSPE, 25 mg/kg CsA and 100 mg/kg GSPE+25 mg/kg CsA, respectively. On day 21, blood samples were taken for blood urea nitrogen (BUN), creatinine and CsA levels, and renal tissue was used for total oxidant system (TOS), total anti-oxidant system (TAS), oxidative stress index (OSI) and malondialdehyde (MDA) measurements. In addition to renal histopathology, apoptosis staining was performed on renal tissue. RESULTS: The BUN, creatinine, TOS, OSI, MDA, histopathological score, and apoptotic index exhibited increases in the CsA group. In the CsA+GSPE group, however, BUN, creatinine, OSI, MDA, renal histopathological score and apoptotic index (AI) decreased and TAS levels increased. In addition, there was no difference between the CsA and CsA+GSPE groups with regard to CsA levels. CONCLUSION: We demonstrated that GSPE prevents CsA nephropathy and that this effect is achieved by anti-apoptotic and anti-oxidant activity. We also achieved a significant recovery in kidney functions without affecting CsA plasma levels.

The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy.

BACKGROUND/AIMS: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. METHODS: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. RESULTS: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. CONCLUSION: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

Antiapoptotic and antioxidant effects of GSPE in preventing cyclosporine A-induced cardiotoxicity.

OBJECTIVES: Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity. MATERIALS AND METHODS: Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. RESULTS: The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase. CONCLUSION: In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities.

Empirical therapy for male factor infertility: Survey of the current practice.

BACKGROUND: Empirical therapy is sometimes used by urologists who desire to improve the outcomes for infertility patients. However, the literature on empirical therapies is scarce. Therefore, we aimed to assess the clinical practice of urologists regarding the use of empirical therapy in the treatment of infertility patients. METHODOLOGY: An online survey using Google Forms was used to collect data during the Saudi Urological Association Annual Meeting, February 2019. Additional data were gathered electronically in March and April 2019 and sent to respondents. The study was closed in May 2019. No incentives were provided to the respondents. RESULTS: A total of 96 (80%) urologists participated in the survey, of whom 69.8% were consultants, and 20.8% were andrology-trained urologists. Empirical therapy was used by 86.5% of urologists for patients with idiopathic oligoasthenoteratozoospermia. The most commonly used empirical therapies were zinc, L-canitine, clomiphene citrate, and L-arginine. The main factors that influenced the selection of empirical therapy were follicle-stimulating hormone, total testosterone, and luteinizing hormone levels. CONCLUSION: Empirical therapy was used by more than three-quarters of the participants for idiopathic male infertility. There were no clear guidelines for the ideal therapy to be considered for individual patients while treating empirically. Our concern is that urologists use a wide variety of medications without significant data to support these medications.

Role of erythropoietin in prevention of amikacin-induced nephropathy.

BACKGROUND: Aminoglycoside antibiotics are widely used potent bactericidal drugs. However, nephrotoxicity side effects via oxidant injury limit their effectiveness. Erythropoietin (Epo) has been shown to exert pleiotropic effects besides promoting erythrocyte differentiation such as antiapoptotic, antioxidant functions in ischemic and toxic acute renal injury. Therefore we aimed to explore whether Epo is renoprotective in an amikacin-induced nephropathy model in rats. METHODS: Twenty-eight rats were distributed equally into 4 groups: (i) injected with saline, (ii) injected with amikacin (1.2 g/kg intraperitoneally [i.p.]), (iii) pretreated with Epo (2,000 IU/kg, i.p.) and amikacin (1.2 g/kg i.p.) and (iv) injected only with Epo (2,000 IU/kg, i.p.). Twenty-four hours after last injection, renal tissues were excised for histopathological examinations, and blood samples were collected for serum creatinine and blood urea nitrogen measurements. RESULTS: An approximately twofold elevation in blood urea nitrogen concentration in the amikacin group (26.6 ± 3.9 mg/dL) compared with saline group (13.1 ± 0.4 mg/dL) was found, reflecting a significant degree of renal dysfunction (p<0.01). Serum urea levels were significantly improved in rats pretreated with Epo (15.9 ± 0.9 mg/dL). The most severe and pronounced injuries based on tubular necrosis were observed in the amikacin group, while rats pretreated with Epo demonstrated marked reduction of the histological features of renal injury. CONCLUSION: As far as we know, the present results are the first to demonstrate a protective effect of exogenous Epo against experimental amikacin-induced renal injury. According to these results, Epo may improve the therapeutic potential of amikacin. More studies are needed for a final conclusion.