N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency

Calderón Guzmán, David; Osnaya Brizuela, Norma; Ortíz Herrera, Maribel; Valenzuela Peraza, Armando; Labra Ruíz, Norma; Juárez Olguín, Hugo; Santamaria del Angel, Daniel; Barragán Mejía, Gerardo

doi:10.3390/ijms25116239

Open AccessArticle

N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency

by

David Calderón Guzmán

¹,

Norma Osnaya Brizuela

¹

,

Maribel Ortíz Herrera

²,

Armando Valenzuela Peraza

¹,

Norma Labra Ruíz

¹,

Hugo Juárez Olguín

^3,*

,

Daniel Santamaria del Angel

¹

and

Gerardo Barragán Mejía

²

¹

Laboratory of Neurosciences, Instituto Nacional de Pediatria (INP), Mexico City 04530, Mexico

²

Laboratory of Experimental Bacteriology, Instituto Nacional de Pediatria INP, Mexico City 04530, Mexico

³

Laboratory of Pharmacology, Instituto Nacional de Pediatría, Avenida Imán N° 1, 3rd piso Colonia Cuicuilco, Mexico City 04530, Mexico

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2024, 25(11), 6239; https://doi.org/10.3390/ijms25116239

Submission received: 12 April 2024 / Revised: 15 May 2024 / Accepted: 17 May 2024 / Published: 5 June 2024

(This article belongs to the Section Biochemistry)

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Abstract

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

Keywords: antioxidant biomarkers; cisplatin; N-acetylcysteine; glutathione; malnutrition

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MDPI and ACS Style

Calderón Guzmán, D.; Osnaya Brizuela, N.; Ortíz Herrera, M.; Valenzuela Peraza, A.; Labra Ruíz, N.; Juárez Olguín, H.; Santamaria del Angel, D.; Barragán Mejía, G. N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency. Int. J. Mol. Sci. 2024, 25, 6239. https://doi.org/10.3390/ijms25116239

AMA Style

Calderón Guzmán D, Osnaya Brizuela N, Ortíz Herrera M, Valenzuela Peraza A, Labra Ruíz N, Juárez Olguín H, Santamaria del Angel D, Barragán Mejía G. N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency. International Journal of Molecular Sciences. 2024; 25(11):6239. https://doi.org/10.3390/ijms25116239

Chicago/Turabian Style

Calderón Guzmán, David, Norma Osnaya Brizuela, Maribel Ortíz Herrera, Armando Valenzuela Peraza, Norma Labra Ruíz, Hugo Juárez Olguín, Daniel Santamaria del Angel, and Gerardo Barragán Mejía. 2024. "N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency" International Journal of Molecular Sciences 25, no. 11: 6239. https://doi.org/10.3390/ijms25116239

APA Style

Calderón Guzmán, D., Osnaya Brizuela, N., Ortíz Herrera, M., Valenzuela Peraza, A., Labra Ruíz, N., Juárez Olguín, H., Santamaria del Angel, D., & Barragán Mejía, G. (2024). N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency. International Journal of Molecular Sciences, 25(11), 6239. https://doi.org/10.3390/ijms25116239

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N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency

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