Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat’s Heart

Bukhari, Ishfaq A.; Mohamed, Osama Y; Alhowikan, Abdulrahman Mohammed; Lateef, R; Hagar, Hanan; Assiri, Raghad A; Alqahtani, Wa’ad Massoud A

doi:10.7759/cureus.21572

Cited by 7 publications

(2 citation statements)

References 22 publications

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“…PCNA contributes to ADMSC proliferation and resistance to apoptosis. Similarly, (Chen, Wang et al, 2015& Meligy, El-Deen Mohammed et al, 2022 Bukhari, Mohamed et al (2022).…”

Section: Discussionmentioning

confidence: 96%

Adipose Tissue-Mesenchymal Stem Cells Improve Cisplatin-Induced Cardiotoxicity in Rats Via Modulating Apoptosis, Oxidative Stress, Inflammation, and Angiogenesis

Rateb

Gomaa²,

Hussein³

2022

Egyptian Academic Journal of Biological Sciences, D. Histology

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Background: Cardiotoxicity is a common adverse reaction to cisplatin treatment. Not all the mechanisms underlying cisplatin-induced cardiotoxicity have been described. Stem cells have been acknowledged as a potentially effective, novel treatment approach in treating several diseases. Objective: The current study was done to assess the impact of adipose mesenchymal stem cells (ADMSCs) in repairing cardiac damage induced by cisplatin and to investigate the underlying mechanisms.Materials and Methods: 32 rats were utilized for this study. They were randomly classified into four equal groups: the Control group that received saline intraperitoneally (i.p.), the Cisplatin-treated group that received a single i.p. injection of cisplatin at a dose of 7 mg/kg and was left for 5 days, Stem celltreated group that administered cisplatin as before and after 5 days they received a single dose of ADMSCs (1 × 10 6 ) mL injected intravenously and were left for 60 days after cell injection, and the Withdrawal group that received cisplatin in same dose and manner of administration as above and then left for 65 days. At the end of the experiment, the portions of the heart specimen were used to determine the levels of Total antioxidant capacity (TAC), cardiac Malondialdehyde (MDA), Tumur nuclear factor-α (TNF-α), and interleukin 2 (IL-2). The remaining portions of the heart muscle were prepared for histological and immunohistochemistry studies. Results: Cisplatin treated group revealed extensively disrupted organization of muscle fibers that appeared remarkably damaged with focal lysis with the widening of the spaces among the myofibrils, severely distorted nuclei which appeared highly condensed and had irregular malformed shapes with severe mitochondrial changes. Also, the levels of proinflammatory cytokines e.g., TNF-α and IL-2 were increased in the cardiac tissue. Also, increased MDA and decreased TAC levels were detected. Injection of ADMSCs ameliorated cardiotoxicity induced by cisplatin via suppression of oxidative injury, inhibition of pro-inflammatory cytokines, suppression of apoptotic cascades, and activation of angiogenesis. Conclusion: This study could be considered preliminary in proving that AD-MSCs therapy has a promising role to enhance marked regeneration of cisplatin-induced myocardial injury.

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“…PCNA contributes to ADMSC proliferation and resistance to apoptosis. Similarly, (Chen, Wang et al, 2015& Meligy, El-Deen Mohammed et al, 2022 Bukhari, Mohamed et al (2022).…”

Section: Discussionmentioning

confidence: 96%

Adipose Tissue-Mesenchymal Stem Cells Improve Cisplatin-Induced Cardiotoxicity in Rats Via Modulating Apoptosis, Oxidative Stress, Inflammation, and Angiogenesis

Rateb

Gomaa²,

Hussein³

2022

Egyptian Academic Journal of Biological Sciences, D. Histology

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“…The level of hyperlactatemia and the extent of acidemia haven't demonstrated any predictive capacity, despite being markers of metformin toxicity. Irrespective of the toxicity's origin, the treatment should encompass supportive measures and the assessment of additional therapies such as gastrointestinal cleansing, glucose and insulin administration, alkalinization, and extracorporeal techniques to reduce metformin levels in the body and restore metabolic balance [7]. The assessment of the potential toxicity of the newly developed drug rutin trihydrate involved the measurement of motility at 96 hours post-fertilisation (hpf).…”

Section: Introductionmentioning

confidence: 99%

Neurotoxicity Evaluation of Rutin Trihydrate vs. Metformin in Zebrafish Larvae: A Comparative Risk Assessment Study

Tejaswini,

Praveen Kumar

2024

E3S Web Conf.

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To examine the neurotoxicity induced by the novel drug Rutin trihydrate and metformin in the zebrafish larvae model. Test solutions for the exposure groups were prepared by diluting the stock solution with egg water. These solutions contained 30 µM metformin in combination with 9.5 µM of the innovative drug rutin trihydrate. Maintenance of zebrafish and egg collection: Breeding groups were chambered in a specific spawning tank in a male-to-female ratio of 1:1. The spawning tank is provided with a box and with mesh as the bottom base to collect the zebrafish embryos and to protect the zebrafish embryos from the adult fish. Embryotoxicity assay: This work includes 2 groups and a total sample size of 30. Group 1 underwent examination using the novel drug Rutin trihydrate, which exhibits solubility in 0.01% of Dimethyl sulfoxide (DMSO), while Group 2 was subjected to examination using metformin, soluble in 100µl of DMSO (Dimethyl sulfoxide) combined with 99% water, both assessments conducted on larval zebrafish. Embryos were segregated for each exposure in groups in petri plates with n= 15 embryos per plate and were exposed to the novel drug Rutin trihydrate from 4 - 96 hpf (Hours Post Fertilization). Other conditions required for the validation of this study were maintained as stated by the OECD (Organization for Economic All the experiments were carried out in triplicate. Statistical analysis: SPSS software facilitated the determination of statistical significance between the two groups. The parameters adhered to a confidential ratio of 95%, a threshold of 0.05, G power at 80%, and an enrolment ratio of 1. Results indicated a significant neuroprotective effect of rutin trihydrate-treated larvae (27.77±1.15) compared to metformin-treated larvae (18.0±0.68), displaying a statistical significance of p = 0.000 (p < 0.05).

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Edaravone and obeticholic acid protect against cisplatin-induced heart toxicity by suppressing oxidative stress and inflammation and modulating Nrf2, TLR4/p38MAPK, and JAK1/STAT3/NF-κB signals

El-Shoura,

Hassanein,

Taha

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Cardiotoxicity is a significant adverse effect of cisplatin (CIS) that necessitates extensive medical care. The current study examines the cardioprotective effects of edaravone (EDV), obeticholic acid (OCA), and their combinations on CIS-induced cardiac damage. Rats were allocated into five groups: the normal control group, the remaining four groups received CIS (7.5 mg/kg, i.p.) as a single dose on the fifth day and were assigned to CIS, OCA (10 mg/kg/day) + CIS, EDV (20 mg/kg/day) + CIS, and the (EDV + OCA) + CIS group. Compared to the CIS-treated group, co-treating rats with EDV, OCA, or their combinations significantly decreased ALP, AST, LDH, CK-MB, and troponin-I serum levels and alleviated histopathological heart abnormalities. Biochemically, EDV, OCA, and EDV plus OCA administration mitigated cardiac oxidative stress as indicated by a marked decrease in heart MDA content with a rise in cardiac antioxidants SOD and GSH associated with upregulating Nrf2, PPARγ, and SIRT1 expression. Besides, it dampened inflammation by decreasing cardiac levels of TNF-α, IL-1β, and IL-6, mediated by suppressing NF-κB, JAK1/STAT3, and TLR4/p38MAPK signal activation. Notably, rats co-administered with EDV plus OCA showed noticeable protection that exceeded that of EDV and OCA alone. In conclusion, our study provided that EDV, OCA, and their combinations effectively attenuated CIS-induced cardiac intoxication by activating Nrf2, PPARγ, and SIRT1 signals and downregulating NF-κB, JAK1/STAT3, and TLR4/p38MAPK signals. Graphical Abstract Outlined diagram summarized the possible protective mechanisms of OCA and/or EDV against cisplatin-induced cardiac injury

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Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat’s Heart

Cited by 7 publications

References 22 publications

Adipose Tissue-Mesenchymal Stem Cells Improve Cisplatin-Induced Cardiotoxicity in Rats Via Modulating Apoptosis, Oxidative Stress, Inflammation, and Angiogenesis

Adipose Tissue-Mesenchymal Stem Cells Improve Cisplatin-Induced Cardiotoxicity in Rats Via Modulating Apoptosis, Oxidative Stress, Inflammation, and Angiogenesis

Neurotoxicity Evaluation of Rutin Trihydrate vs. Metformin in Zebrafish Larvae: A Comparative Risk Assessment Study

Edaravone and obeticholic acid protect against cisplatin-induced heart toxicity by suppressing oxidative stress and inflammation and modulating Nrf2, TLR4/p38MAPK, and JAK1/STAT3/NF-κB signals

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