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Effects of NO modulators and antioxidants on endocrine and cellular markers in rats under repetitive restraint stress

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Abstract

The aim of the study was to evaluate the effects of NO modulators and antioxidant treatments on endocrine (plasma corticosterone), cellular (heat shock protein 70 [HSP-70] and nuclear factor κB [NF-κB]), and oxidative stress markers in repetitively stressed rats. Repetitive (restraint) stress (RS 1hr/day × 21 days) enhanced the levels of cellular and endocrine stress markers in the rat blood and altered pro-oxidant-antioxidant balance differentially in the control and test groups. Exposure to repetitive RS enhanced malondialdehyde (MDA) levels, lowered reduced glutathione (GSH), and superoxide dismutase (SOD) levels as well as nitric oxide (NOx) levels. NO precursor L-arginine and NO synthase inhibitors were found to differentially modulate stress-induced mechanism in altering NF-κB, HSP-70, and corticosterone levels. The antioxidant L-ascorbic acid (L-AA) significantly suppressed RS(×21)-induced elevation of NF-κB and HSP-70 levels, depicting protective effects, as also evidenced by reversal of elevated corticosterone levels. The results suggest that NO modulators and antioxidants differentially influence repetitive stress-induced changes in endocrine and cellular markers, and the complex interaction between NO and cellular markers like HSP70 and NF-κB plays a crucial modulatory role in this phenomenon.

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Authors and Affiliations

  1. Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India

    Giridhari Pal

  2. Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia

    Khalid Anwer & Abdullah Alshetaili

  3. VSS Medical College, Sambalpur University, Sambalpur, Odisha, India

    Jyotirmoyee Jena

  4. Chitkara College of Pharmacy, Chitkara University, Chandigarh, Punjab, India

    Aayush Sehgal, Sukhbir Singh, Neelam Sharma & Tapan Behl

  5. School of Pharmaceutical Sciences, Shoolini University, Solan, India

    Aditi Sharma

  6. Department of Human Anatomy, College of Medicine, Taif University, Taif, Saudi Arabia

    Ashraf Al-Brakati

  7. Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania

    Simona Bungau

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  1. Giridhari Pal
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  2. Khalid Anwer
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Contributions

Conceptualization, GP and TB; writing—original draft preparation, GP, TB, MKA, AA and JJ; literature review: AS, SS, NS, AS; proof read, AAB and SB.

Corresponding authors

Correspondence to Giridhari Pal or Tapan Behl.

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Ethics approval was taken from institutional animal ethical committee and also guidelines of Ministry of Environment and Forests, Government of India, and Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) were followed.

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Pal, ., Anwer, K., Alshetaili, A. et al. Effects of NO modulators and antioxidants on endocrine and cellular markers in rats under repetitive restraint stress. Environ Sci Pollut Res 29, 12043–12053 (2022). https://doi.org/10.1007/s11356-021-16592-6

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