Downregulation of redox imbalance and iNOS/NF-ĸB/caspase-3 signalling with zinc supplementation prevents urotoxicity of cyclophosphamide-induced hemorrhagic cystitis in rats

Famurewa, Ademola C.; Edeogu, Chuks Oswald; Offor, Florence I.; Besong, E E; Akunna, G.G.; Maduagwuna, Ekenechukwu K.

doi:10.1016/j.lfs.2020.118913

Cited by 22 publications

(23 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decrease in antioxidants in the renal cells of the rats treated with CP alone was an indication of redox-homeostasis imbalance. CP has been previously shown to induce oxidative damage, inflammation, and cell necrosis or apoptosis after activation and promotion of reactive oxygen species (ROS) via its metabolite, acrolein [ 7 , 11 , 14 ], which subsequently trigger the deactivation and diminishing of antioxidant defense capacities of the affected organisms [ 10 , 11 , 45 ]. In this study, the overproduction of ROS outweighs the endogenous antioxidant capacity, triggers oxidative stress, and subsequently damages renal cells of the CP-treated rats as was reflected by the increased levels of markers of oxidative stress and decreased levels of antioxidant parameters.…”

Section: Discussionmentioning

confidence: 99%

“…The CP active metabolite, 4-Hydroxycyclophosphamide, is partially tautomerized into aldosphosphamide, which in turn is broken down by phosphatase in the circulation and live cell and give rise to two cytotoxic metabolites, phosphoramide mustard and acrolein [ 6 ]. The therapeutic action of phosphoramide mustard has been previously reported to be responsible for anti-tumor effects [ 6 ], while acrolein is responsible for cytotoxic effects of CP, such as hemorrhagic cystitis during the drug administration [ 2 , 7 ]. The CP toxic metabolite damages the living tissues by abating the tissue endogenous antioxidant system through the generation of reactive oxygen free radicals which are mutagenic to living cells.…”

Section: Introductionmentioning

confidence: 99%

“…Administration of high dose of CP has been reported to increase lipid peroxidation and causes reduction in the endogenous enzymatic and non-enzymatic antioxidants [ 7 , 8 ]. Previous studies have described the beneficial uses of antioxidants substances along with chemotherapy in preventing the drugs side effect on the body tissues [ 7 , 9 , 10 ]. The antioxidant agent like kolaviron proved effective in the prevention of CP cardiotoxicity in rats [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Polyphenol-rich extract of Ocimum gratissimum leaves prevented toxic effects of cyclophosphamide on the kidney function of Wistar rats

Alabi

Akomolafe

Omole

et al. 2021

BMC Complement Med Ther

View full text Add to dashboard Cite

Background Cyclophosphamide (CP) is one of the potent and low cost chemotherapy used in clinical setting against a variety of tumors. However, its association with nephrotoxicity limits its therapeutic use. Ocimum gratissimum leaf is a medicinal plant with numerous pharmacological and therapeutic efficacies, such as antioxidant, anti-inflammation, and anti-apoptotic properties. Methods The present study was designed to evaluate the protective effect of Ocimum gratissimum (OG) against CP-induced kidney dysfunction in rats. Rats were pre-treated with 400 mg/kg b.w. of leave extract of Ocimum gratissimum (Ocimum G.) for 4 days and then 50 mg/kg b.w. of CP was co-administered from day 5 to day 7 along with Ocimum G. Markers of renal function and oxidative stress, food and water intake, electrolytes, aldosterone, leukocytes infiltration, inflammation and histopathological alteration were evaluated. Results Obvious renal inflammation and kidney injuries were observed in CP treated groups. However, administration of leave extract of Ocimum G. prevented oxidative stress, kidney injuries, attenuated inflammation, increased aldosterone production and reduced sodium ion and water loss in rats. The plasma creatinine, urea and urine albumin concentration were normalized after the administration of Ocimum G. extract in rats treated with CP. Ocimum G. also decreased the plasma concentrations of Interleukin-(IL)-6, C-reactive protein and activity of myeloperoxidase and malondialdehyde in CP treated rats. Conclusion Ocimum G. prevented kidney injury and enhanced renal function via inhibiting inflammation and oxidant-induced CP toxicity. The efficacy of Ocimum G. is related to the presence of various phytochemicals in the plant.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polyphenol-rich extract of Ocimum gratissimum leaves prevented toxic effects of cyclophosphamide on the kidney function of Wistar rats

Alabi

Akomolafe

Omole

et al. 2021

BMC Complement Med Ther

View full text Add to dashboard Cite

show abstract

“…51 Increasing volume of evidence has strongly suggested that oxidative stress is a prime trigger for pro-inflammatory cascades. 32,53,54 In fact, the crosstalks between oxidative stress and inflammatory response are two linked pathways in DN pathophysiology, which are considered to be a major hallmark of DN. On the one hand, however, the renal histopathology of the untreated DN rats revealed vacuolated cytoplasm, tubule basement thickening and glomerular https://doi.org/10.2147/DMSO.S302748…”

Section: Discussionmentioning

confidence: 99%

Antidiabetic and Nephroprotective Effects of Polysaccharide Extract from the Seaweed Caulerpa racemosa in High Fructose-Streptozotocin Induced Diabetic Nephropathy

Cao¹,

Li²,

Famurewa³

et al. 2021

DMSO

View full text Add to dashboard Cite

Background: Nephropathy is a frontline complication of diabetes mellitus (DM) associated with impaired redox-inflammatory networks. The study investigated the antidiabetic and nephroprotective potentials of PCR against diabetic nephropathy (DN) in rats. Methods: DN was induced in rats using a combination of a high fructose solution for 4 weeks and an intraperitoneal injection of streptozotocin (35 mg/kg). Diabetic rats were treated with PCR (100 and 400 mg/kg body weight) for 8 weeks. Serum biochemical parameters as well as renal oxidative stress parameters, proinflammatory cytokines, Western blot and histopathological analyses were evaluated. Results: There were significant increases in fasting blood glucose, urinary albumin, serum creatinine, blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), and lowdensity lipoproteins (LDL-C) levels in diabetic rats compared to the non-diabetic control rats. DM-induced DN prominently depressed renal superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, whereas renal malondialdehyde (MDA) level was markedly increased. Furthermore, renal inflammatory cytokines, IL-1β, IL-6, TNF-α and TGF-β, were considerably elevated compared to non-diabetic control rats. Additionally, DN rats showed a significant increase in renal fibrosis, as evidenced by increased expression of TGF-β1, collagen-1, fibronectin and alpha-smooth muscle actin (α-SMA) in the kidneys. Histopathological lesions were consistent with tubule thickening and glomerular hypertrophy. Conversely, PCR treatment exerted significant attenuation of hyperglycemia, dyslipidemia and renal oxidative stress indicators. The increased renal levels of IL-1β, IL-6, TNF-α and TGF-β were also notably reversed dose-dependently with alleviation of nephropathic histology. Furthermore, PCR reduced the expression of α-SMA, fibronectin, collagen-1 and TGF-β1 in the renal tissues. Conclusion:Our results suggest that PCR displayed antidiabetic and nephroprotective effects against DN by impeding oxidative stress and inflammation. As such, PCR has potentials as a food supplement for alleviating renal dysfunction caused by diabetes.

show abstract

“…These inflammatory markers are well-recognized markers of bladder inflammmation in rodents since both protein levels and mRNA levels increase in the bladder in different models of bladder inflammation (including chemical cystitis, e.g. cyclophosphamide/ifosfamide; common methods of experimental cystitis) [36][37][38][39][40][41]. Thus measuring protein and mRNA levels in the bladder is a reliable and accepted method for examing inflammatory changes in the bladder caused by our bladder pain model.…”

Section: Plos Onementioning

confidence: 99%

Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain

Mahmood

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

Background Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalgesia. Since MIF binds to multiple receptors, we investigated the contribution of individual urothelial MIF receptors to PAR4-induced HMGB1 release in vivo and in vitro and bladder pain in vivo. Methodology/Principal findings We tested the effect of intravesical pre-treatment with individual MIF or MIF receptor (CD74, CXCR4, CXCR2) antagonists on PAR4-induced HMGB1 release in vivo (female C57/BL6 mice) and in vitro (primary human urothelial cells) and on PAR4-induced bladder hyperalgesia in vivo (mice). In mice, PAR4 induced HMGB1 release and bladder hyperalgesia through activation of intravesical MIF receptors, CD74 and CXCR4. CXCR2 was not involved in these effects. In primary urothelial cells, PAR4-induced HMGB1 release through activation of CD74 receptors. Micturition parameters in mice were not changed by any of the treatments. Conclusions/Significance Urothelial MIF receptors CD74 and CXCR4 mediate bladder pain through release of urothelial HMGB1. This mechanism may set up persistent pain loops in the bladder and warrants further investigation. Urothelial CD74 and CXCR4 may provide novel targets for interrupting bladder pain.

show abstract

Downregulation of redox imbalance and iNOS/NF-ĸB/caspase-3 signalling with zinc supplementation prevents urotoxicity of cyclophosphamide-induced hemorrhagic cystitis in rats

Cited by 22 publications

References 44 publications

Polyphenol-rich extract of Ocimum gratissimum leaves prevented toxic effects of cyclophosphamide on the kidney function of Wistar rats

Polyphenol-rich extract of Ocimum gratissimum leaves prevented toxic effects of cyclophosphamide on the kidney function of Wistar rats

Antidiabetic and Nephroprotective Effects of Polysaccharide Extract from the Seaweed Caulerpa racemosa in High Fructose-Streptozotocin Induced Diabetic Nephropathy

Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain

Contact Info

Product

Resources

About