ayad ali hussein ameen

Nephrotoxicity is a major dose-limiting side effect facing cisplatin-based chemotherapy of a wide variety of cancers. Oxidative stress plays an important role in mechanisms responsible for nephrotoxicity. This study was to examine the antioxidant properties of Lcarnitine in protection from nephrotoxicity due to cisplatin. 32 patients were enrolled in the study and were randomized into two groups. Only 28 patients were eligible and successfully completed treatment cycles. In group I, (N=14) patients received six cycles of cisplatin based regimen with 21 days-intervals. In group II, (N=14) patients received L-carnitine plus cisplatin based regimen. Serum creatinine and cystatin C were measured at base line and 21 days after 1, 2, 4 and 6 cycles while urinary malondialdehyde was measured at base line and 1 day after 1, 2, 4 and 6 cycles of cisplatin based regimen. Group I, cisplatin caused significant (P<0.05) increment in serum creatinine, serum cystatin C and urinary malondialdehyde in comparison to base line levels. Serum creatinine and cystatin C and urinary malondialdehyde level of group II was significantly (P<0.05) lower than that of group I. L-carnitine significantly ameliorated nephrotoxicity in patients receiving cisplatin primarily by inhibiting renal oxidative stress.

Cisplatin is a potent antitumor agent that is useful in chemotherapy of various types of cancers. Currently, nephrotoxicity limits its usefulness. The main mechanism responsible for nephrotoxicity is oxidative stress with associated inflammation. This study was to evaluate the protective effect of zinc sulphate on cisplatin-induced nephrotoxicity in cancer patients. Twenty eight patients were participated in the study and were randomized into two groups. Patients in group I (N=14) received six cycles of cisplatin based regimen every 21 days. Patients in group II (N=14) received zinc sulphate in addition to cisplatin based regimen. Serum cystatin C and cystatin C-based GFR were measured at base line and 21 days after 1, 2, 4 and 6 cycles while urinary malondialdehyde and IL-18 were measured at base line and 1 day after 1, 2, 4 and 6 cycles of cisplatin based regimen. Zinc sulfate addition to cisplatin in group II significantly (P<0.05) ameliorated the cisplatin-induced increment in serum cystatin C, urinary malondialdehyde and IL-18 and the cisplatin-induced decline in cystatin C-based GFR that were demonstrated in group I. The significant protective effect of zinc sulfate on cisplatin-induced nephrotoxicity may be through its antioxidant and anti-inflammatory action.

Abstract Introduction: Acute renal failure (ARF) is an important clinical problem with a high mortality and morbidity. Ischemia/reperfusion (I/R) was considered one of the primary causes of ARF. Inflammatory process is thought to be the major mechanism that contribute to I/R injury. There are evidences of the importance of thyroid hormone (TH) in the response of the myocardium to ischemic stress and cardiac remodeling following myocardial infarction. 3,5-diiodothyropropionic acid (DITPA) is a synthetic TH analogue with a low metabolic activity. Also DITPA have evidences of improving effects on I/R in heart through modulation of cellular signaling in response to ischemic stress and this modulation may be beneficial in protection from renal I/R damage. Objectives: The objective of present study was to assess the effects of DITPA on renal I/R injury and the resulted kidney dysfunction in a mouse model. Materials and Methods: A total of 18 Adult males of Swiss albino mice were randomized to three groups: I/R group (n=6), mice underwent 30 minute bilateral renal ischemia and 48 hr reperfusion. Sham group (n=6), mice underwent same anesthetic and surgical procedures except for ischemia induction. DITPA treated group: (n=6), I/R + DITPA (3.75 mg/kg) by intraperitoneal injection. After the end of reperfusion phase mice were sacrificed, blood samples were collected directly from the heart for determination of serum IL-18, IL-6, urea and Creatinine. Both kidney were excised, the right one homogenized for oxidative stress parameters (MDA and GSH) measurements and the left kidney fixed in formalin for histological examination. Results: Serum IL-18, IL-6, urea and Creatinine, kidney MDA levels and scores of histopathological changes were significantly (P< 0.05) elevated in I/R group as compared with that of sham group. Kidney GSH level was significantly (P < 0.05) decreased in I/R group as compared with that of sham group. DITPA caused non-significant (P>0.05) changes in levels of all study parameters as compared with that of I/R group. Conclusion: The results of the present study show that DITPA insignificantly ameliorated kidney damage resulted from I/R.

Abstract Background: Acute renal failure (ARF) is an important clinical problem with a high mortality and morbidity. One of the primary causes of ARF is ischemia/reperfusion (I/R). Inflammatory process and oxidative stress are thought to be the major mechanisms causing I/R. MK-886 is a potent inhibitor of leukotrienes biosynthesis which may have anti-inflammatory and antioxidant effects through inhibition of polymorphonuclear leukocytes (PMNs) infiltration into renal tissues. 3, 5-diiodothyropropionic acid (DITPA) have evidences of improving effects on I/R in heart through modulation of cellular signaling in response to ischemic stress. The objective of present study was to assess the effects of MK-886 and DITPA on renal I/R injury. Methods: A total of 24 Adult males of Swiss albino mice were randomized to four groups: I/R group (n = 6), mice underwent 30 minute bilateral renal ischemia and 48 hr reperfusion. Sham group (n = 6), mice underwent same anesthetic and surgical procedures except for ischemia induction. MK-886-treated group: (n = 6), I/R + MK-886 (6 mg/kg) by intraperitoneal injection. DITPA-treated group: (n = 6), I/R + DITPA (3.75 mg/kg) by intraperitoneal injection. After the end of reperfusion phase mice were sacrificed, blood samples were collected directly from the heart for determination of serum TNF-a, IL-6, urea and Creatinine. Both kidney were excised, the right one homogenized for oxidative stress parameters (MDA and GSH) measurements and the left kidney fixed in formalin for histological examination. Results: Serum TNF-a, IL-6, urea and Creatinine, kidney MDA levels and scores of histopathological changes were significantly (P < 0.05) elevated in I/R group as compared with that of sham group. Kidney GSH level was significantly (P < 0.05) decreased in I/R group as compared with that of sham group. MK-886 treated group has significantly (P < 0.05) lowered levels of all study parameters except for GSH level which was significantly (P < 0.05) higher as compared with that of I/R group. DITPA caused non-significant (P > 0.05) changes in levels of all study parameters as compared with that of I/R group. Conclusion: The results of the present study show that MK-886 significantly ameliorated kidney damage that resulted from I/R. For DITPA, as its administration might not be successful, administration using a different protocol may give different effects on I/R.