Tenofovir disoproxil fumarate, a nucleotide reverse transcriptase inhibitor utilized for the treatment of hepatitis B virus and human immunodeficiency virus infections; and is now one of the most widely used antiretroviral drug. However, tenofovir disoproxil fumarate can induce nephrotoxicity, which may be attributed to the interaction between such drug and the organic anion transporters (hOAT1, and OAT3) with consequent changes in levels of some parameters that may have a role in nephrotoxicity. Thiazide diuretics have high to intermediate potency of inhibition of OAT1s and OAT3; thus, it may possess nephroprotective effects. This study was designed to investigate whether hydrochlorthiazide has nephroprotective effects on tenofovir disoproxil fumarate-induced nephrotoxicity in rats. Twenty eight healthy adult male albino rats weighing 180-200g were utilized in this study for duration of 5weeks (35 days) treatment. Rats were randomly divided into four groups (7animals each). Group I: Negative control (orally given distilled water) by gavage tube; Group II: Rats orally received 600 mg/kg/day tenofovir disoproxil fumarate by gavage tube; Group III: Rats orally administered hydrochlorothiazide alone at a dose (10 mg/kg/day) by gavage tube, and Group IV: Rats orally administered hydrochlorothiazide at a dose (10 mg/kg/day) plus tenofovir disoproxil fumarate 600 mg/kg/day by gavage tube. On day 36 of the study, after euthanization of each animal by diethyl ether, 3-5ml of blood samples were collected from each rat by an intra-cardiac puncture, then centrifuged at 3000 rpm for 15 minutes to obtain serum, which was then transferred into suitable plain tubes and preserved at -20 °C; and it was utilized for the estimation of cystatin C and IL-10 level. Rats administered tenofovir disoproxil fumarate for 5 weeks (group II) produced a significant -elevation (P<0.05) in serum cystatin C level and –reduction in serum IL-10 levels compared to negative control group (group I); similarly, administration of hydrochlorothiazide alone to rats (group III) produced a significant -elevation (P<0.05) in serum cystatin C level and –reduction in serum IL-10 levels compared to negative control group (group I); also, rats administered combination of hydrochlorothiazide plus tenofovir disoproxil fumarate to rats for 5 weeks (group IV) produced significant elevation (P<0.05) in serum level of cystatin C, and a significant reduction (P<0.05) in IL-10 serum level in treated rats compared to the corresponding levels of negative control animals (group I); beside that in (group IV) rats there were significant reduction (P<0.05) in serum level of both cystatin C, and IL-10 in treated rats compared to the corresponding levels compared to TDF-treated (group II). In conclusion, treatment with hydrochlorthiazide plus tenofovir disoproxil fumarate in an attempt to prevent nephrotoxicity induced by tenofovir disoproxil fumarate is not attained.
Tenofovir disoproxil fumarate, a nucleotide reverse transcriptase inhibitor utilized for the treatment of hepatitis B virus and human immunodeficiency virus infections; and is now one of the most widely used antiretroviral drug. However, tenofovir disoproxil fumarate can induce nephrotoxicity, which may be attributed to the interaction between such drug and the organic anion transporters (hOAT1, and OAT3) with consequent changes in levels of some parameters that may have a role in nephrotoxicity. Thiazide diuretics have high to intermediate potency of inhibition of OAT1s and OAT3; thus, it may possess nephroprotective effects. This study was designed to investigate whether hydrochlorthiazide has nephroprotective effects on tenofovir diso
... Show MoreBackground: Cyclophosphamide is an alkylating agent that is effective against a broad spectrum of tumors, with nephrotoxicity as a side effect. Irigenin is a natural isoflavonoid isolated from the rhizome of Belamcanda chinensis that has been reported to exert antioxidant activities. Objective: Evaluating the possible protective effects of irigenin on cyclophosphamide-induced nephrotoxicity in male rats. Methods: Fifty apparently healthy male albino rats were divided into five groups: (control, induction, irigenin, irigenin with cyclophosphamide, and vitamin E with cyclophosphamide. At the end of the experiment (day 29), all rats were sacrificed. Different parameters were evaluated, including urea and creatinine serum concentration,
... Show MoreDrug –induced nephrotoxicity is an important cause of renal failure. Aminoglycoside antibiotics, such as amikacin, which causes ototoxicity and nephrtotoxicity as a main side effects, this is focused on the use of natural materials as antioxidants against the toxic oxidative action that exert a cell damaging effect. The most important one of these materials is the honey. The aim of this work is to evaluate the antioxidant effects of honey against amikacin – induced nephrotoxicity.18 albino rats divided into 3 groups (6 rats per each group), group 1 received I.P daily dose of normal saline (control), group 2 received (35 mg/kg/day) I.P dose of amikacin ,and group 3 received (35mg/kg/day) of amikacin I.P dose in combina
... Show MoreDrug-induced acute kidney injury is a serious disorder. Oxidative stress has a key role in its initiation and progression. In this study, the possible ameliorative effect of fimasartan against methotrexate-induced nephrotoxicity was investigated in comparison with α-tocopherol in rats. Wistar rats were allocated into six groups and treated as follows: group Ӏ received water on a daily basis for 8 successive days; group ӀӀ received methotrexate (20 mg/kg) on day 1, followed by water for 7 successive days; group ӀӀӀ received fimasartan (3 mg/kg/day) for 7 successive days; group IV received α-tocopherol (1 g/kg/day) for 7 successive days; group V re
... Show MoreAbstract Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rats through the involvement of Nrf2
... Show MoreBoth methotrexate and vitamin D3 are used in combination for the treatment of various diseases. The aim of this study is to highlight the effect of vitamin D3 on methotrexate-induced jejunum damage using biochemical and histopathological studies. Seven groups of both sexes of rats were selected and treated as follows: (Group I and Group II) : control 1,control 2 (I.P normal saline) daily for 14 and 21 days respectively ; (Group III and Group IV) :vitamin D3 groups (500 IU/rat/day) orally for 14 and 21 days, respectively;(Group V): once daily dose of methotrexate 20mg/kg, I.P injected for 4 days;(Group VI):vitamin D3 (500 IU/rat/day) once daily for 14 days and methotrexate (20 mg/kg I.P) injected only at day 10;.(Group
... Show MoreBoth methotrexate and vitamin D3 are used in combination for the treatment of various diseases. The aim of this study is to highlight the effect of vitamin D3 on methotrexate-induced jejunum damage using biochemical and histopathological studies. Seven groups of both sexes of rats were selected and treated as follows: (Group I and Group II) : control 1,control 2 (I.P normal saline) daily for 14 and 21 days respectively ; (Group III and Group IV) :vitamin D3 groups (500 IU/rat/day) orally for 14 and 21 days, respectively;(Group V): once daily dose of methotrexate 20mg/kg, I.P injected for 4 days;(Group VI):vitamin D3 (500 IU/rat/day) once daily for 14 days and methotrexate (20 mg/kg I.P) injected only at day 10;.(Group VII) vit
... Show MoreAbstract
Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rat
... Show More