VASP attenuates lipopolysaccharide-induced renal injury via modulation of TLR4 signaling, inflammation and oxidative stress.

Background

Vasopressin (VASP), also known as antidiuretic hormone, is a peptide hormone that helps regulate water balance and vascular tone. Emerging evidence suggests it also modulates immune responses and circulatory dynamics. Lipopolysaccharide (LPS) is found in the cell membranes of Gram-negative bacteria. It activates TLR4 signalling pathways. Systemic inflammation, oxidative stress, and organ damage occur, and the renals are especially at risk.

Aim

OF STUDY This research investigated the protective effects of VASP on rat renal tissue against LPS-induced inflammation and oxidative stress.

Methods

Adult male rats were randomly assigned to three groups, comprising eight rats each. One group served as a control (no treatment), another received LPS (one intraperitoneal injection of 5 mg/kg, followed by intravenous saline every 12 h for 72 h), and the final group received both LPS and VASP (LPS 5 mg/kg i.p. plus intravenous VASP 0.1 µg/kg every 12 h for 72 h). Renal function was evaluated by measuring blood urea nitrogen (BUN) and serum creatinine levels. We quantified oxidative stress by measuring malondialdehyde (MDA), superoxide dismutase (SOD) activity, and serum nitric oxide (NO). We quantified inflammatory mediators using multiple approaches: we measured renal IL-6 levels by ELISA; assessed HMGB1 expression at both mRNA and protein levels; and evaluated the presence of CD68, TLR4, TNF-α, and IL-1β using immunohistochemistry.

Results

Compared to controls, LPS raised serum creatinine and BUN levels. Additionally, LPS increased oxidative stress, as evidenced by higher serum nitric oxide and renal malondialdehyde levels. This was also linked to decreased superoxide dismutase activity. In addition, LPS significantly increased the levels of inflammatory mediators. The findings demonstrated elevated IL-6 levels, increased HMGB1 mRNA and protein expression, and marked staining for TLR4, TNF-α, IL-1β, and CD68. Histopathology revealed tubular dilation, proteinaceous casts, mononuclear cell infiltration, interstitial oedema, and vascular congestion, consistent with LPS-induced renal damage. VASP markedly diminished these changes. VASP treatment improved renal function, ameliorated inflammation and oxidative stress, and improved the observed tissue changes.

Conclusion

These findings provide preclinical evidence that VASP's protective effects against LPS-induced organ damage are mediated by multiple pathways, suggesting its potential as a therapeutic agent for the role of inflammation-related renal injury, although the specific receptor-mediated mechanisms remain to be established.