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IL-6/STAT3 and adipokine modulation using tocilizumab in rats with fructose-induced metabolic syndrome

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Abstract

Metabolic syndrome (MetS) is a low-grade inflammation state that results from an interplay between genetic and environmental factors. The incidence of MetS among individuals with insulin resistance, dyslipidemia, elevated blood pressure, and obesity, which constitute the syndrome, is 40% in the Middle East. The absence of an approved therapeutic agent for MetS is one reason to investigate tocilizumab (TCZ), which might be effective in the treatment of MetS. Results have implicated interleukin 6 (IL-6) in the development of MetS, identifying inflammation as a critical factor in its etiology and offering hope for new therapeutic approaches development. Here, we evaluate whether tocilizumab can be used for metabolic syndrome treatment. We assigned rats to three groups, 8 rats each: a negative-control group, provided with standard rodent chow and water; a fructose-fed group, provided with standard rodent chow and 10% fructose in drinking water for 22 weeks; and a treatment group, fed as per the metabolic syndrome group but treated with tocilizumab (5 mg/kg/week, intraperitoneal) for the final 5 weeks. Treatment with TCZ successfully ameliorated the damaging effects of fructose by stabilizing body weight gain and through the normalization of serum biochemical parameters and histopathological examination. Significant differences in adipokine levels were perceived, resulting in a significant decline in serum leptin and interleukin 6 (IL-6) levels concurrent with adiponectin normalization. Tocilizumab might be an effective agent for the treatment of metabolic syndrome. However, further investigations on human subjects are needed before the clinical application of tocilizumab for this indication.

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Abbreviations

MetS:

Metabolic syndrome

IL-6:

Interleukin 6

TCZ:

Tocilizumab

ALT:

Alanine aminotransaminase

AST:

Aspartate aminotransaminase

HDL:

High-density lipoprotein

H&E:

Hematoxylin-eosin stain

LDL:

Low-density lipoprotein

i.p.:

Intraperitoneal

HOMA-IR:

Hemostatic Model Assessment of Insulin Resistance

GSH:

Reduced glutathione

MDA:

Malondialdehyde

MTC:

Masson’s trichrome

SBP:

Systolic blood pressure

IR:

Insulin receptor

STAT3:

Signal transducer and activator of transcription 3

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University for Technology and Information, Al-Mokattam, Cairo, Egypt

    Haneen Yahia

  2. Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt

    Azza Hassan

  3. Department of Biochemistry, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt

    Mona R. El-Ansary

  4. School of Pharmacy, Newgiza University, Giza, Egypt

    Muhammad Y. Al-Shorbagy

  5. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Muhammad Y. Al-Shorbagy & Mohamed F. El-Yamany

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  1. Haneen Yahia
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  4. Muhammad Y. Al-Shorbagy
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  5. Mohamed F. El-Yamany
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Contributions

HY: conceptualization, formal analysis, funding acquisition, conducted experiments, and writing—original draft. AH: investigation, conducted experiments, and review and editing. M.R.E: formal analysis, funding acquisition, and review and editing. M.Y.A: conceptualization, formal analysis, and writing—review and editing. M.F.E: conceptualization, writing—review and editing, and supervision. All authors read and approved the manuscript. All data were generated in-house and no paper mill was used.

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Yahia, H., Hassan, A., El-Ansary, M.R. et al. IL-6/STAT3 and adipokine modulation using tocilizumab in rats with fructose-induced metabolic syndrome. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2279–2292 (2020). https://doi.org/10.1007/s00210-020-01940-z

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