Cyanocobalamin (vitamin B12) ameliorates lipopolysaccharide-induced systemic and lung inflammation in rats

Sep 30, 2026

Study evaluates cyanocobalamin (vitamin B12) effects on systemic and lung injury markers in lipopolysaccharide (LPS)-challenged rats. Forty male Wistar rats received vehicle, LPS, or LPS plus cyanocobalamin (0.25, 0.5, or 1 mg/kg) orally from days 1–16; blood and lung samples were analyzed. LPS increased leukocyte counts and proinflammatory mediators (IL-6, TNF-α, IL-1β), oxidative stress indices (NO, MDA), and apoptosis-related expression (Bax, p53, Bax/Bcl-2), while reducing Bcl-2 and antioxidant defenses (thiols, CAT, SOD). Cyanocobalamin dose-dependently attenuated lung inflammation, apoptosis, and oxidative stress.

LanguageEnglish

CategoryHealthcare

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[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Cyanocobalamin (vitamin B12) ameliorates lipopolysaccharideinduced systemic and lung inflammation in rats FereshtehAsgharzadeh1,2, Aliye Ghorbanpour1, Zahra Khosravi3, Rasul Saberi3 & Zahra Gholamnezhad1,2􀀍 Considering the antioxidant and immunomodulatory properties of vitamin B12, this study aimed to evaluate the effects of cyanocobalamin (vitamin B12) on systemic and lung injury markers induced by lipopolysaccharide (LPS). Forty male Wistar rats were randomly assigned to five groups: Control; LPS (1 mg/kg, intraperitoneal injection on day 3 and from days 8 to 16); and LPS treated with cyanocobalamin at doses of 0.25, 0.5, and 1 mg/kg. Cyanocobalamin was administered orally from days 1 to 16. Finally, blood and lung tissue samples were collected to evaluate systemic and lung injury markers. Total white blood cell (WBC), neutrophil, eosinophil, and monocyte counts, as well as serum interleukin-6 (IL-6) levels, were elevated in LPS group compared to control animals. Treatment with cyanocobalamin at all doses reduced total WBC, neutrophil, and lymphocyte counts relative to the LPS group, except for total WBC atthe 0.5 mg/kg dose. LPS induced upregulation of nitric oxide (NO), IL-6, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), malondialdehyde (MDA), and the expression of Bax, p53, and the Bax/Bcl-2 ratio, along with histopathological injury. Conversely, it downregulated Bcl-2 expression, total thiol content, and catalase (CAT) and superoxide dismutase (SOD) activities in lung tissue compared to controls. Cyanocobalamin dose-dependently ameliorated LPS-induced lung alterations, including IL-6, TNF-α, MDA, thiol content, Bax, p53, Bax/Bcl-2 ratio expression, CAT activity, and injury score. These findings suggest that a synthetic form of vitamin B12, cyanocobalamin, ameliorates LPS-induced leukocytosis, lung inflammation, apoptosis, and oxidative stress. Keywords Lipopolysaccharide, Cyanocobalamin, Vitamin B12, Systemic, Inflammation, Apoptosis, Lung injury Systemic inflammation plays a central role in the pathogenesis of numerous acute and chronic diseases, including sepsis, acute lung injury (ALI), and multiple organ dysfunction syndrome1. A well-established experimental model for studying systemic and pulmonary inflammation involves the use of lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria2,3. LPS activates Toll-like receptor 4 (TLR4), initiating a cascade of proinflammatory responses, including the release of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), as well as reactive oxygen and nitrogen species (ROS/ RNS). These events ultimately lead to systemic inflammatory response syndrome (SIRS) and tissue damage2,4,5. Vitamin B12 (cyanocobalamin) is a vital cofactor in various metabolic processes, including DNA synthesis and methylation reactions. Recent studies have highlighted its emerging role in modulating oxidative stress and immune responses, particularly in inflammatory lung conditions. Cyanocobalamin possesses antioxidant properties that help neutralize ROS and suppress lipid peroxidation, both of which contributing to lung tissue damage during systemic inflammation6,7. Vitamin B12 has been proposed as an immunotherapeutic agent8. It has been demonstrated that vitamin B12 deficiency, combined with imbalanced folic acid levels, may result in reduced lymphocyte counts and diminished natural killer cell activity in patients9. Furthermore, vitamin B12 has been shown to reduce the expression of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β in experimental 1Applied Biomedical Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran. 2Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran. 3Psychiatry and Behavioral Scie

FAQs

How was cyanocobalamin administered in the rat study?

Cyanocobalamin was given orally from day 1 to day 16 to rats in the LPS plus cyanocobalamin groups at doses of 0.25, 0.5, or 1 mg/kg.

What inflammatory and injury markers did LPS increase?

LPS elevated total WBC and differential counts, serum IL-6, and upregulated nitric oxide (NO), IL-6, TNF-α, IL-1β, MDA, and apoptosis-related factors including Bax, p53, and the Bax/Bcl-2 ratio.

What effects did cyanocobalamin have on LPS-induced lung changes?

Cyanocobalamin reduced LPS-induced leukocytosis and dose-dependently ameliorated lung inflammation, oxidative stress, and apoptosis-related alterations, including improvements in IL-6, TNF-α, MDA, thiol content, CAT activity, SOD activity, and injury score.

Sep 30, 2026

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