Cyclophosphamide (CP), a bifunctional alkylating agent used in chemotherapy has been reported to induce organ toxicity mediated by generation of reactive oxygen species and oxidative stress. Gallic acid (GA), a phenolic substance, is a natural antioxidant with proven free radical scavenging activity and offers protection against oxidative damage. This research study was designed to investigate the ameliorative effect of GA against CP-induced toxicity in rats. Twenty-five male Wistar rats (180–200 g) were randomized into five treatment groups: (A) control, (B) CP, 2 mg/kg body weight (b.w.), (C) pre-treatment with GA (20 mg/kg b.w.) for seven days followed by CP (2 mg/kg b.w.) for seven days, (D) co-treatment with GA (20 mg/kg b.w) and CP (2 mg/kg b.w.) for seven days, and (E) GA (20 mg/kg b.w.) for seven days. CP induced marked renal and hepatic damages as plasma levels of urea, creatinine, bilirubin and activities of AST, ALT, ALP and GGT were significantly elevated (p < 0.05) in the CP-treated group relative to control. In addition, hepatic levels of GSH, vitamin C and activities of SOD, catalase and GST significantly reduced in the CP-treated group when compared with control. This was accompanied with a significant increase in hepatic lipid peroxidation. The restoration of the markers of renal and hepatic damages as well as antioxidant indices and lipid peroxidation by pre- and co-treatment with GA clearly shows that GA offers ameliorative effect by scavenging the reactive oxygen species generated by CP. This protective effect may be attributed to the antioxidant property of gllic acid.
We investigated the protective effect of gallic acid (GA) against methotrexate (MTX)-induced hepatotoxicity and nephrotoxicity. Male Wistar rats were randomized into five groups (n = 6/group): I, control; II, MTX-treated for seven days; III, pre-treated with GA for seven days, followed by MTX for seven days; IV, co-treated with MTX and GA for seven days and V, GA for seven days. MTX caused a significant increase (P<0.05) in plasma biomarkers of nephrotoxicity (urea, creatinine) and hepatotoxicity (Bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase) when compared with control. Furthermore, MTX caused a significant decrease in the activities of hepatic enzymic antioxidants (superoxide dismutase, catalase, glutathione S-transferase) and nonenzymic antioxidants (Vitamin C and glutathione), followed by a significant increase in hepatic malondialdehyde content. However, pretreatment and co-treatment with gallic acid ameliorated the MTX-induced biochemical changes observed. Taken together, GA protected against MTX-induced hepatotoxicity and nephrotoxicity in rats, by reducing the impact of oxidative damage to tissues.
One major challenge with the use of anticancer agents is the phenomenon of drug-induced toxicity. Melphalan (MPLN) is an alkylating anticancer agent, while quercetin (QCT) is an antioxidant. We investigated the protective role of quercetin against MPLN-induced toxicity. Twenty-five male Wistar rats (160–170 g) were randomized into five treatment groups; (I) control, (II) MPLN (0.2 mg/kg b.w.), (III) pre-treated with QCT (20 mg/kg b.w.) for 7 days followed by MPLN (0.2 mg/kg b.w.) for 7 days, (IV) cotreated with QCT (20 mg/kg b.w.) and MPLN (0.2 mg/kg b.w.) for 7 days, and (V) QCT (20 mg/kg b.w.) alone. MPLN caused a significant increase in plasma bilirubin, urea, and creatinine by 122.2%, 102.3%, and 188%, respectively (P < 0.05). Similarly, plasma ALP, ALT, AST, and γ-GT activities increased significantly by 57.9%, 144.3%, 71.3%, and 307.2%, respectively, relative to control. However, pre or cotreatment with QCT ameliorated the levels of renal and hepatic function indices. Hepatic ascorbic acid and GSH and activities of glutathione-S-transferase, SOD, and catalase decreased significantly by 36.2%, 188%, 46.5%, 34.4%, and 55.2%, respectively, followed by increase in MDA content by 46.5% relative to control. Pre- and cotreatment with QCT reestablished the hepatic antioxidant status and lipid peroxidation. Overall, quercetin protected against MPLN-induced renal and hepatic toxicity in rats.
Background:Procarbazine (PCZ) is an effective chemotherapeutic drug used in the treatment of lymphoma; however, oxidative stress–mediated testicular toxicity is a major side effect. Recently, therapeutic intervention using flavonoids against oxidative stress–related pathologies is gaining more attention. Morin (MOR) is a natural flavonoid with proven antioxidant activity. This study was designed therefore to evaluate the potential role of MOR in ameliorating PCZ-induced testicular oxidative stress and altered sperm quality in rat model.Methods:A total of 24 male Wistar rats (170–180 g) were randomly assigned into 4 treatment groups: I, control; II, PCZ (2 mg/kg b.w.); III, PCZ (2 mg/kg b.w.) + MOR (100 mg/kg b.w.) simultaneously administered and IV, MOR (100 mg/kg b.w.), and all treatments lasted 14 days.Results:PCZ treatment displayed significant reduction in sperm number, sperm motility, percentage normal sperm cells, and daily sperm production rate. Meanwhile the activities of testicular enzymes: gamma-glutamyl transferase, acid phosphatase, and lactate dehydrogenase were significantly altered in the PCZ group compared to control. Furthermore, PCZ caused a significant reduction in levels of glutathione and ascorbic acid as well as activities superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase in the testes of PCZ-treated rats. A significant increase in testicular malondialdehyde level was also observed in the PCZ group. MOR treatment, however, significantly restored the altered sperm parameters and biochemical markers in the testis.Conclusions:Our data suggest that MOR administration protected against PCZ-induced testicular and spermatotoxicity in rat, by improving testicular antioxidant system.
Haloxyfop-p-methyl ester (HPME) ((R)-2-{4-[3-chloro-5-(trifluoromethyl)-2-pyridyloxy]phenoxy}propionic acid), is a selective aryloxyphenoxypropionate (AOPP) herbicide. It exerts phytotoxicity through inhibition of lipid metabolism and induction of oxidative stress in susceptible plants. This study investigated the toxicological potentials of HPME in rats. Twenty-four male Wistar rats (170–210 g) were randomized into four groups (I–IV). Group I (control) received 1 mL of distilled water, while animals in Groups II, III and IV received 6.75, 13.5 and 27 mg/kg body weight HPME, respectively, for 21 days. There was a significant (p < 0.05) increase in renal and hepatic function biomarkers (urea, creatinine, total bilirubin, ALP, ALT, AST) in the plasma of treated animals compared to control. Levels of testicular antioxidants, ascorbic acid and glutathione, and activities of glutathione-S-transferase, superoxide dismutase and catalase were reduced significantly after 21 days of HPME administration in a dose-dependent manner. The testicular malondialdehyde level increased significantly in the HPME-treated rats relative to the control. A significant decrease in testicular lactate dehydrogenase, acid phosphatase and γ-glutamyl transferase was also observed in HPME-treated animals. Testicular histology revealed severe interstitial edema and sections of seminiferous tubules with necrotic and eroded germinal epithelium in the HPME-treated rats. Overall, data from this study suggest that HPME altered hepatic and renal function and induced oxidative stress and morphological changes in the testis of rats.
Levofloxacin (LFX) is a broad spectrum fluoroquinolone antibiotic used in the treatment of infections such as pneumonia, chronic bronchitis, and sinusitis. The present study assessed the likely toxic effect of LFX on hepatic and renal tissues in rats. Twenty male Wistar rats were randomly divided into four treatment groups: A: control, B: 5 mg/kg bw LFX (half therapeutic dose), C: 10 mg/kg bw LFX (therapeutic dose), and D: 20 mg/kg bw LFX (double therapeutic dose). After seven days of administration, result indicated significant(P<0.05)increase in plasma ALT, AST, and ALP activities in the treated groups compared to control. Also, there was a significant increase in plasma creatinine, urea, and total bilirubin in the treated groups relative to control. Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides also increased significantly in the treated groups relative to control. Also, hepatic MDA level increased significantly in all the treated groups. However, hepatic SOD, catalase, and GST activities were significantly reduced in the LFX-treated animals. Moreover, GSH and ascorbic acid levels were significantly decreased in the LFX-treated groups relative to control. In conclusion, three doses of levofloxacin depleted antioxidant defense system and induced oxidative stress and hepatic and renal dysfunctions in rats.
Procarbazine (PCZ) (indicated in Hodgkin’s disease), is an alkylating agent known to generate free radicals in vivo, while Quercetin (QCT) is a flavonoid antioxidant with proven free radical scavenging capacity. This study investigated the protective effects of QCT on PCZ-induced oxidative damage in the rat. Male Wistar rats (160–180 g) were randomized into five groups (n = 5/group): I (control), II PCZ-treated (2 mg/kg body weight (bw) for seven days); III pre-treated with QCT (20 mg/kg bw) for seven days, followed by PCZ for seven days; IV co-treated with PCZ and QCT for seven days and V administered QCT alone for seven days. PCZ caused a significant increase in plasma total bilirubin, urea, and creatinine when compared with control (P < 0.05). Similarly, plasma activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GT) were significantly increased in the PCZ-treated group relative to control. Furthermore, PCZ caused a significant decrease in the activities of hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) as well as levels of ascorbic acid (AA) and glutathione (GSH). This was followed by a significant increase in hepatic malondialdehyde (MDA) content. However, QCT pre-treatment and co-treatment ameliorated the PCZ-induced changes in plasma levels of urea, creatinine, and bilirubin as well as the activities of ALP, AST, ALT, and GGT. QCT also ameliorated hepatic AA and GSH levels and the activities of SOD, CAT, and GST. This all suggests that QCT protected against PCZ-induced oxidative damage in rats.
Chlorambucil (4-[4-[bis(2-chloroethyl)amino]phenyl]butanoic acid) is an alkylating agent, indicated in chronic lymphocytic leukaemia. Kolaviron (KV), a biflavonoid complex from Garcinia kola, and L-ascorbic acid (AA) are known to protect against oxidative damage in vivo. This study evaluates the protective capacity of KV and AA on chlorambucil-induced oxidative stress in the testes of rat. Twenty male Wistar rats (180–200 g) were randomized into four groups: I: control, II: chlorambucil (0.2 mg/kg b.w.), III: 0.2 mg/kg chlorambucil and 100 mg/kg KV, and IV: 0.2 mg/kg chlorambucil and 100 mg/kg AA. After 14 days of treatments, results indicated that chlorambucil caused significant reduction (P < 0.05) in testicular vitamin C and glutathione by 32% and 39%, respectively, relative to control. Similarly, activities of testicular GST, SOD, and CAT reduced significantly by 48%, 47%, and 49%, respectively, in chlorambucil-treated rats relative to control. Testicular MDA and activities of ALP, LDH, and ACP were increased significantly by 53%, 51%, 64%, and 70%, respectively, in the chlorambucil-treated rat. However, cotreatment with KV and AA offered protection and restored the levels of vitamin C, GSH, and MDA as well as SOD, CAT, GST, ACP, ALP, and LDH activities. Overall, kolaviron and L-ascorbic acid protected against chlorambucil-induced damage in the testes of the rat.
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