Ameliorative effect of herbacetin against cyclophosphamide-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction

Ojo

2023

Preprint

Quercetin's antioxidative properties make it of potential benefit in many clinical conditions where oxidative stress is implicated in the pathological processes. To investigate the possible protective effects of quercetin on neurobehaviour, brain oxidative status, markers of inflammation, neurotransmitter balance and astrocyte immunoreactivity in healthy rats administered cyclophosphamide. Sixty rats were randomly assigned into six groups. Groups A and D served as normal and cyclophosphamide control respectively and were fed standard rat chow, groups B and E were fed quercetin supplemented diet (100 mg/kg of feed), while those in groups C and F were fed quercetin supplemented diet at 200 mg/kg of feed. Animals in group A to C also received intraperitoneal normal saline on days 1 and 2, while those in groups D-F got intraperitoneal cyclophosphamide (150 mg/kg/day on days 1 and 2). Standard diet and quercetin supplemented diet were administered daily for 21 days. At the end of the experimental period, behavioural tests were carried out, following which animals were sacrificed and blood taken for the assessment of biochemical parameters. Organs were either homogenised or processed for histological study. Quercetin mitigated CYP induced weight loss and reduction in food consumption. It also improved total antioxidant capacity while reducing CYP induced lipid peroxidation and biochemical markers of impaired liver function. A reduction in CYP induced increase in urea and creatinine was also observed. Interleukin 10 increased, while the CYP induced increase in interleukin 1 beta and TNF alpha were also mitigated following quercetin administration. Open field exploratory activities and grooming increased with CYP and the lowest dose of quercetin. The anxiolytic effects of quercetin was demonstrable in the elevated plus maze; while its memory-enhancing effects were seen in the Y-maze and radial-arm maze. Finally, quercetin improved acetylcholine dopamine levels and brain-derived neurotropic factor, while reducing serotonin levels and astrocyte immunoreactivity. The results show quercetin s ability to protect against CYP induced changes in rats. They also highlight the possible use of quercetin as a possible adjunct in cancer chemotherapy induced tissue damage. However, further research will be needed to delineate its exact role in cancer chemotherapy.

Section: Discussionmentioning

confidence: 96%

Biflavonoid quercetin protects against cyclophosphamide–induced organ toxicities via modulation of inflammatory cytokines, brain neurotransmitters, and astrocyte immunoreactivity

Ojo

2023

Preprint

“…Accordingly, numerous researchers have shown the antiradical potentials of PN in previously published reports. 33,60,61 Moreover, Ijaz et al 29 reported significant radical quenching activity of PN in cadmium-mediated oxidative stress in rats represented by an upsurge in the CAT, GSR, SOD and GSH-PX and down-modulation of MDA levels.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to our data, researchers have reported the positive modulation of inflammatory cytokines (IL-1b, TNF-α, NF-kB, inducible NOS and COX-2) by PN supplementation. 29 Moreover, a recent molecular docking study revealed that PN can bind to myeloid differentiation factor (MD2) and Toll-like receptor 4 (TLR4) without requiring of hydrogen bonds. Moreover, researchers declared that PN fits with LYS89 in MD2 via carbon hydrogen and many non-covalent bonds, thereby inhibiting LPS linkage between MD2 and TLR4 and lowering the rate of TLR4/MD2-mediated inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

“…Pinostrobin (5-hydroxy-7-methoxy flavanone; PN) is a member of flavonoids and an ether (Figure 1) and a dietary bioflavonoid isolated from natural resources including plants, Pinus strobus , 4 Cajanus cajan (L.), 25 rhizomes of Boesenbergia rotunda 26 and finger root (Boesenbergia rotunda) . 27 Numerous biological potentials exhibited by this flavanone including antioxidants, 28 anti-inflammatory, 29 augmentations of inflammatory cytokines (interleukin-1β, tumour necrosis factor (TNF)-α) 30 and anti-ulcerogenic actions. 26 Moreover, in vitro , studies revealed outstanding inhibitory efficacy of PN against the growth of breast cancer, 31 cervical, 32 lung cancers, 33 HL-60 and K562 leukaemia cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pinostrobin attenuates azoxymethane-induced colorectal cytotoxicity in rats through augmentation of apoptotic Bax/Bcl-2 proteins and antioxidants

Ali Abed Wahab,

Ain Salehen,

Abdulla

et al. 2023

SAGE Open Medicine

Objectives: Pinostrobin (5-hydroxy-7-methoxyflavanone; PN) is a natural active ingredient with numerous biological activities extensively utilized in tumour chemotherapy. The present study investigates the chemo-preventive potentials of PN on azoxymethane-mediated colonic aberrant crypt foci in rats. Methods: Sprague Dawley rats clustered into five groups, normal control (A) and cancer controls were subcutaneously injected with normal saline and 15 mg/kg azoxymethane, respectively, and nourished on 10% tween 20 and fed on 10% tween 20; reference control (C), injected with 15 mg/kg azoxymethane and injected (intraperitoneal) with 35 mg/kg 5-fluorouracil (5-FU); D and E rat groups received a subcutaneous injection of 15 mg/kg azoxymethane and nourished on 30 and 60 mg/kg of PN, respectively. Results: The acute toxicity trial showed a lack of any abnormal signs or mortality in rats ingested with 250 and 500 mg/kg of PN. The gross morphology of colon tissues revealed significantly lower total colonic aberrant crypt foci incidence in PN-treated rats than that of cancer controls. Histological examination of colon tissues showed increased aberrant crypt foci availability with bizarrely elongated nuclei, stratified cells and higher depletion of the submucosal glands in cancer controls. PN treatment caused positive modulation of apoptotic (Bax and Bcl-2) proteins and inflammatory cytokines (TNF-α, IL-6 and IL-10). Moreover, rats fed on PN had significantly higher antioxidants (superoxide dismutase) and lower malondialdehyde concentrations in their colon tissue homogenates. Conclusion: The chemoprotective efficiency of PN against azoxymethane-induced aberrant crypt foci is shown by lower aberrant crypt foci values and higher aberrant crypt foci inhibition percentage, possibly through augmentation of genes responsible for apoptotic cascade and inflammations originating from azoxymethane oxidative stress insults.

“…7 Preclinical evidence also emphasizes the increased apoptosis where increased caspases, cytochrome C, dysfunctional mitochondria, and calcium overload were found. 4,5,7,8 In addition to increased oxidative stress, inflammation, and apoptosis, CPM administration is also reported to cause renal fibrosis and increased levels of transforming growth factor beta 1 (TGF-β1). 6 Hence, a multifactorial approach exists for the management of CPM-induced nephrotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Nephroprotective Effect of Bergapten Against Cyclophosphamide-Mediated Renal Stress, Inflammation, and Fibrosis in Wistar Rats: Probable Role of NF-kB and TGF-β1 Signaling Molecules

Mohsin,

Akhtar,

Alkahtani

et al. 2024

ACS Omega

Cyclophosphamide (CPM) is a well-established antineoplastic drug with marked clinical outcomes in various types of cancers. Despite being a promising drug, its use is associated with significant renal toxicity and often limits its use, leading to compromised clinical outcomes. Therefore, this study explored the renal protective effect of bergapten (BGP), a natural bioactive compound that showed marked antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. Till now, BGP has not been studied for its renal protective effect in an in vivo model. Animals were divided into control, toxic, BGP-3, BGP-10, and BGP Per se. The control group was treated with normal saline for 2 weeks. To the toxic group, CPM 200 mg/kg was given on day 7 as i.p. To BGP-3, 10, and Per se, BGP-3 and 10 mg/kg, ip was given 2 weeks with a single shot of CPM 200 day 7. To the Per se group, only BGP 10 mg/kg, ip was given from day 1 to day 14. After 14 days, animals were sacrificed, and kidneys were removed and studied for the markers of oxidative stress, inflammation, renal injury, renal fibrosis, and renal damage using biochemical, histopathological, and immunohistochemical studies. We found that BGP-10 effectively reversed the damage toward normal, whereas BGP-3 failed to exhibit a significant renal protective effect. We conclude that bergapten could be a potential renal protective drug, and hence, more detailed cellular molecular-based studies are needed to bring this drug from the bench to the bedside.