Cisplatin toxicity in the developing brain displays an absolute requirement for caspase-3

Hui, Kelvin; Latif, Maya; Soeandy, Chesa Dojo; Huang, Sophia; Rodgers, Christopher E.; Elia, Andrew; Henderson, Jeffrey T.

doi:10.1016/j.expneurol.2022.114010

Cited by 8 publications

(6 citation statements)

References 32 publications

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“…Caspase-3 activity and the levels of PUMA, p53 and p21 Cip1 were found to be elevated when cells were exposed to cisplatin alone indicating genotoxic stress. In line with our findings, a recent paper by Hui et al (2022) indicated that caspase 3 induction is necessary to for cisplatin-induced apoptosis in a neurotoxicity model and is considered a reliable marker for neuronal cell death ( Hui et al, 2022 ). Several other studies unveiled the significance of the pro-apoptotic gene (PUMA) in neurodegeneration ( Maor-Nof et al, 2016 ; Simon et al, 2016 ).…”

Section: Discussionsupporting

confidence: 91%

Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin

Alotaibi

Al-Aqil

Alqahtani

et al. 2022

Front. Aging Neurosci.

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Platinum-based chemotherapeutic treatment of cancer patients is associated with debilitating adverse effects. Several adverse effects have been well investigated, and can be managed satisfactorily, but chemotherapy-induced peripheral neuropathy (CIPN) remains poorly treated. Our primary aim in this study was to investigate the neuroprotective effect of the immunomodulatory drug rapamycin in the mitigation of cisplatin-induced neurotoxicity. Pain assays were performed in vivo to determine whether rapamycin would prevent or significantly decrease cisplatin-induced neurotoxicity in adult male Balb/c mice. Neuropathic pain induced by both chronic and acute exposure to cisplatin was measured by hot plate assay, cold plate assay, tail-flick test, and plantar test. Rapamycin co-treatment resulted in significant reduction in cisplatin-induced nociceptive-like symptoms. To understand the underlying mechanisms behind rapamycin-mediated neuroprotection, we investigated its effect on certain inflammatory mediators implicated in the propagation of chemotherapy-induced neurotoxicity. Interestingly, cisplatin was found to significantly increase peripheral IL-17A expression and CD8- T cells, which were remarkably reversed by the pre-treatment of mice with rapamycin. In addition, rapamycin reduced the cisplatin-induced neuronal apoptosis marked by decreased neuronal caspase-3 activity. The rapamycin neuroprotective effect was also associated with reversal of the changes in protein expression of p21Cip1, p53, and PUMA. Collectively, rapamycin alleviated some features of cisplatin-induced neurotoxicity in mice and can be further investigated for the treatment of cisplatin-induced peripheral neuropathy.

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Section: Discussionsupporting

confidence: 91%

Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin

Alotaibi

Al-Aqil

Alqahtani

et al. 2022

Front. Aging Neurosci.

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“… 53 Data from the literature have shown that CIS administration causes caspase‐3 activation leading to apoptosis in the brain and is considered an important parameter in detecting brain damage. 54 , 55 In this study, CIS administration to mice significantly increased caspase‐3 immunoreactivity in brain tissue, whereas tangeretin administration caused a significant decrease in caspase‐3 immunoreactivity. The results of this study suggest a possible relationship between inhibition of caspase‐3‐mediated apoptotic signalling and the neuroprotective effect of tangeretin.…”

Section: Discussionmentioning

confidence: 48%

Effect of tangeretin on cisplatin‐induced oxido‐inflammatory brain damage in rats

Cicek,

Danisman,

Bolat

et al. 2024

J Cellular Molecular Medi

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Cisplatin (CIS) is a platinum‐derived chemotherapeutic agent commonly utilized in the treatment of various malignant tumours. However, anticancer doses of the drug cause serious damage to the brain. This study aimed to determine the potential protective effects of tangeretin, which has antioxidant and anti‐inflammatory properties, in cisplatin‐induced neurotoxicity on BALB/c mice brains. Male BALB/c mice were randomized and separated into four groups. Tangeretin was given for 10 days by gavage. CIS was injected as a single dose of 10 mg/kg intraperitoneally (ip) on the 10th day. Brain tissues, malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and nitric oxide (NO) levels were measured to determine oxidative damage and myeloperoxidase, tumour necrosis factor‐alpha (TNF‐α), interleukin 1 beta (IL‐1β), IL‐6 and IL‐10 were measured to determine inflammatory activity. In addition, 8‐OHdG and caspase‐3 were analysed by immunofluorescence methods. While CIS administration remarkably elevated reactive oxygen species, MDA, and NO levels in brain tissue compared to the control, tGSH, GPx, SOD and CAT levels were significantly decreased. Also, it has been detected that TNF‐α, IL‐1β and IL‐6 obtained in CIS‐treated groups increased as well as IL‐10 decreased, thereby elevating the inflammatory response. In addition, 8‐OHdG and caspase‐3 immunoreactivity in neurons increased with CIS administration. Treatment with tangeretin ameliorated the deterioration in oxidant/antioxidant status, overpowered neuroinflammation and ameliorated neurotoxicity‐induced apoptosis. This study shows that tangeretin has beneficial effects on CIS‐induced neurodegeneration. Possible mechanisms underlying these beneficial effects include the antioxidant and anti‐inflammatory properties of tangeretin.

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“…One of the common adverse effects of oncologic drugs is neurological dysfunction. Cisplatin is a member of a widely utilized class of chemotherapeutic agent that induce DNA damage response, cell cycle arrest, and p53-dependent apoptotic cell death in concert with DNA-platinum adduct formation, and normal programmed cell death (PCD) as oxidative damage [27]. In this work, the use of CDDP in the treatment of the young animals, fed with protein deficient diet, decreased lipid peroxidation levels, glutathione (GSH) and hydrogen peroxide (H2O2) in cerebellum, cortex and medulla oblongata.…”

Section: Discussionmentioning

confidence: 99%

N-acetylcysteine Attenuates Cisplatin Toxicity in Cerebrum and Lung of Young Rats with Artificially Produced Protein Deficiency

Calderon Guzman,

Osnaya Brizuela,

Ortiz Herrera

et al. 2024

Preprint

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Neurotoxicity is a major obstacle to the effectiveness of cisplatin (CDDP) in cancer chemotherapy. In this process, oxidative stress and inflammation are considered to be the major mechanisms involved. The aim was to study the influence of protein quantity on some oxidative parameters in brain and lung of rats treated with cisplatin and N-Acetylcysteine (NAC). Four groups of Wistar rats (6 each one) were fed with a protein diet at 7% for 15 days. Thereafter, the groups were given either a unique dose of cisplatin® 5mg/kg or Acetylcysteine® 5mg/kg as follows: group 1 (control), NaCl 0.9% vehicle; group 2, Cisplatin; group 3, NAC; and group 4, NAC + Cisplatin. The animals were sacrificed, a sample of blood were used to measure blood triglycerides and glucose. The brain and lung were used to assay lipids peroxidation (TBARS), glutathione (GSH), serotonin metabolite (5-HIAA), catalase and the activity of Ca+2, Mg+2 ATPase, using validated methods. TBARS, H2O2 and GSH decreased significantly in cortex and cerebellum/medulla oblongata of groups treated with CDDP and NAC. Total ATPase showed a significant increase in the lung and cerebellum/medulla oblongata, while 5-HIAA depicted the same tendency in cortex of the same group of animals. 5-HIAA and ATPase increase during NAC and Cisplatin administration resulted in brain protection. This effect could even be more powerful when membrane fluidity is increased; thus, proving the efficacy of combined NAC and CDDP drug therapy, which appears to be a promising strategy for future chemotherapy in malnourished patients.

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Cisplatin toxicity in the developing brain displays an absolute requirement for caspase-3

Cited by 8 publications

References 32 publications

Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin

Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin

Effect of tangeretin on cisplatin‐induced oxido‐inflammatory brain damage in rats

N-acetylcysteine Attenuates Cisplatin Toxicity in Cerebrum and Lung of Young Rats with Artificially Produced Protein Deficiency

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