Vitamin D and lactoferrin attenuate stress‐induced colitis in Wistar rats via enhancing AMPK expression with inhibiting mTOR–STAT3 signaling and modulating autophagy. (1st January 2023)

• Record Type: Journal Article
• Authors: Abdelmalak, Marian F. L.; Abdelrahim, Dina S.; George Michael, Tari M. A.; Abdel‐Maksoud, Omnia M.; Labib, Jolly M. W.
• Is Part Of: Cell biochemistry and function. Volume 41:Number 2(2023)
• Page Start: 211
• Page End: 222
• Publication Date: 2023-01-01
• Subjects: AMPK–mTOR–STAT3 signaling -- autophagy -- irritable bowel syndrome -- lactoferrin -- vitamin D3 -- wrap‐restraint stress; Cytochemistry -- Periodicals; Cell metabolism -- Periodicals; Biochemistry -- Periodicals; Cytology -- Periodicals; 572
• DOI: 10.1002/cbf.3774
• Languages: English
• ISSNs: 0263-6484

Abstract

Abstract: Irritable bowel syndrome (IBS) is a global gastrointestinal disorder closely related to psychological stress exposure and local colonic inflammation. Herein, we investigated the effect of wrap‐restraint stress (WRS) on rat behavior, on adenosine monophosphate‐activated protein kinase–mammalian/mechanistic target of rapamycin–signal transducer and activator of transcription 3 (AMPK–mTOR–STAT3) signaling, and autophagy in colonic mucosa. The impact of chronic administration of vitamin D3 and lactoferrin was compared. Twenty‐four male Wistar rats were randomly divided into four groups. Chronic WRS protocol was applied as a rodent model of IBS. Group I: naïve animals, Group II: WRS animals, Group III: WRS‐exposed and treated with vitamin D3 (500 IU/kg/day), and Group IV: WRS‐exposed and treated with lactoferrin (300 mg/kg/day). In this study, we found that chronic administration of each of vitamin D3 and lactoferrin resulted in a significant increase in social interaction test, interleukin‐10, AMPK, optical density of LC3B, goblet cell count and marked decrease in serum cortisol level, STAT3, inflammatory cell count, and optical density of mTOR in comparison to the WRS rats. Our findings suggest that both vitamin D3 and Lactoferrin could augment colonic autophagy through enhanced AMPK expression and inhibition of mTOR–STAT3 signaling, which offers practical insights into their clinical use in the prevention and therapy of IBS. However, lactoferrin intake as a nutritional supplement could be more helpful for stress‐induced colitis treatment than vitamin D3. Significance Statement: Irritable bowel syndrome is a common disease whose incidence is uprising due to chronic life stressors exposure. The need for the intake of dietary supplements that could alleviate IBS symptoms has long been proposed. In the present study, we compared the chronic oral intake of vitamin D3 to lactoferrin in animals exposed to experimental colitis and examined their effects at behavioral and tissue levels. We investigated their effects on the adenosine monophosphate‐activated protein kinase–mammalian/mechanistic target of rapamycin–signal transducer and activator of transcription (AMPK–mTOR–STAT3) signaling and autophagy as a trial to give us more understanding about the molecular pathology of IBS in the colon. Both drugs improved colitis, through lactoferrin seemed more effective. Future research could be directed to explore other drugs that target AMPK–mTOR–STAT3 signaling and autophagy to lessen IBS patients suffering.