International immunopharmacology · 2024
Chronic artificial light exposure in daytime and reversed light: Dark cycle inhibit anti-apoptotic cytokines and defect Bcl-2 in peripheral lymphoid tissues during acute systemic inflammatory response to lipopolysaccharide.
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Madbouly Neveen Adel, Kamal Sahar Mostafa, El-Amir Azza Mohamed
Аннотация
AIMS: The disturbed light: dark (LD) cycle has been associated with critical complications, including obesity, diabetes and cancer. In the present study, we investigated the chronic effects of artificial light at daytime (AL) and light at night (RAL) after intraperitoneal (i.p.) injection of saline and 0.5 mg/kg lipopolysaccharide (LPS) in male Wistar rats.
METHODS: Liver and kidney parameters, fasting blood glucose (FBG), melatonin level, immunohistochemical examinations of B-cell lymphoma-2 (Bcl-2) in spleen and mesenteric lymph and serum antiapoptotic cytokines [interleukin (IL-) 2, 7 and 1].
KEY FINDINGS: After 16 weeks of a daily disturbed LD cycle, RAL increased body weight, upgraded FBG and altered liver and kidney functions with surprisingly increased daytime plasma melatonin. AL + LPS and RAL + LPS rats suffered significantly higher oxidative-nitrosative stress compared to NL + LPS. Oxidative-nitrosative stress was associated with multi-organ inflammation in hepatic, renal, pancreatic, splenic and mesenteric lymph node tissues due to LPS-induced endotoxemia. Anti-apoptotic Bcl-2 activity in peripheral lymphoid organs (spleen and mesenteric lymph node) was lowered due to AL and RAL regimens. At the same pattern, lowering of antiapoptotic serum levels of IL-2, IL-7 and IL-15 indicate alteration of cell cycle and the shifted ability of cells to undergo apoptosis due to abnormal light pollution.
SIGNIFICANCE: Here, the increased lymphocyte apoptosis in lymphoid tissues due to disturbed LD cycle defects the host defense, dysregulates the inflammatory immune response and dysregulates the immune tolerance during acute systemic inflammation due to LPS.
METHODS: Liver and kidney parameters, fasting blood glucose (FBG), melatonin level, immunohistochemical examinations of B-cell lymphoma-2 (Bcl-2) in spleen and mesenteric lymph and serum antiapoptotic cytokines [interleukin (IL-) 2, 7 and 1].
KEY FINDINGS: After 16 weeks of a daily disturbed LD cycle, RAL increased body weight, upgraded FBG and altered liver and kidney functions with surprisingly increased daytime plasma melatonin. AL + LPS and RAL + LPS rats suffered significantly higher oxidative-nitrosative stress compared to NL + LPS. Oxidative-nitrosative stress was associated with multi-organ inflammation in hepatic, renal, pancreatic, splenic and mesenteric lymph node tissues due to LPS-induced endotoxemia. Anti-apoptotic Bcl-2 activity in peripheral lymphoid organs (spleen and mesenteric lymph node) was lowered due to AL and RAL regimens. At the same pattern, lowering of antiapoptotic serum levels of IL-2, IL-7 and IL-15 indicate alteration of cell cycle and the shifted ability of cells to undergo apoptosis due to abnormal light pollution.
SIGNIFICANCE: Here, the increased lymphocyte apoptosis in lymphoid tissues due to disturbed LD cycle defects the host defense, dysregulates the inflammatory immune response and dysregulates the immune tolerance during acute systemic inflammation due to LPS.