Prevention of aspirin-mediated secondary toxicity by combined treatment of carotenoids in macrophages

Kariyappa Vijay; Rudrappa Ambedkar; Poorigali Raghavendra-Rao Sowmya; Suresh Ramaiah; Ambati Ranga Rao; Rohit Gundamaraju; Manjunatha Hanumanthappa; M B Malarvili; Rishya Manikam; Rangaswamy Lakshminarayana

doi:10.1007/s13205-023-03632-w

Prevention of aspirin-mediated secondary toxicity by combined treatment of carotenoids in macrophages

3 Biotech. 2023 Jul;13(7):223. doi: 10.1007/s13205-023-03632-w. Epub 2023 Jun 6.

Affiliations

¹ Department of Microbiology and Biotechnology, Jnana Bharathi Campus, Bangalore University, Bangalore, 560 056 India.
² Department of Statistics, Jnana Bharathi Campus, Bangalore University, Bangalore, 560 056 India.
³ Department of Biotechnology, Vignan's Foundation of Science, Technology and Research (Deemed to be University), Vadlamudi, Guntur, Andhra Pradesh 522213 India.
⁴ ER Stress and Mucosal Immunology Lab, School of Health Sciences, University of Tasmania, Launceston, TAS 7248 Australia.
⁵ Department of Biochemistry, Jnana Bharathi Campus, Bangalore University, Bangalore, 560 056 India.
⁶ Trauma and Emergency, University of Malaya, Kuala Lumpur, Malaysia.
⁷ School of Biomedical and Health Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor Bahru Malaysia.

Abstract

Upon understanding the boosting role of carotenoids on the endogenous anti-inflammatory system, it is vital to explore their role in reducing the use of high doses of non-steroidal anti-inflammatory drug (NSAIDs), and their mediated secondary toxicity during the treatment of chronic diseases. The current study investigates the carotenoids potential on inhibition of secondary complications induced by NSAIDs, aspirin (ASA) against lipopolysaccharide (LPS) stimulated inflammation. Initially, this study evaluated a minimal cytotoxic dose of ASA and carotenoids (β-carotene, BC/lutein, LUT/astaxanthin, AST/fucoxanthin FUCO) in Raw 264.7, U937, and peripheral blood mononuclear cells (PBMCs). In all three cells, carotenoids + ASA treatment reduced the LDH release, NO, and PGE2 efficiently than an equivalent dose of carotenoid or ASA treated alone. Based on cytotoxicity and sensitivity results, RAW 264.7 cells were selected for further cell-based assay. Among carotenoids, FUCO + ASA exhibited an efficient reduction of LDH release, NO, and PGE2 than the other carotenoids (BC + ASA, LUT + ASA, and AST + ASA) treatment. FUCO + ASA combination decreased LPS/ASA induced oxidative stress, pro-inflammatory mediators (iNOS, COX-2, and NF-κB), and cytokines (IL-6, TNF-α, and IL-1β) efficiently. Further, apoptosis was inhibited by 69.2% in FUCO + ASA, and 46.7% in ASA than LPS treated cells. A drastic decrease in intracellular ROS generation with the increase in GSH was observed in FUCO + ASA compared to LPS/ASA groups. The results documented on the low dose of ASA with a relative physiological concentration of FUCO suggested greater importance for alleviating secondary complications and optimize prolonged chronic disease treatments with NSAID's associated side effects.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-023-03632-w.

Keywords: Aspirin; Carotenoids; Macrophages; Reactive oxygen species; Secondary toxicity.

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