Abstract: Objective: To investigate the protective effect of L-theanine (LT) against renal fibrosis in mice exposed to a high-salt diet (HSD, 8% NaCl) for 2 weeks. Methods: A total of 28 four-week-old SPF-grade C57BL/6J male mice were randomly divided into four groups: control, HSD, HSD + low-dose L-theanine (LLT, 10 mg/kg), and HSD + high-dose L-theanine (HLT, 50 mg/kg). Body mass, food intake, water intake, blood pressure, and heart rate were recorded periodically. Serum creatinine (SCr) and inflammatory cytokine levels, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), were determined. Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were used for renal histopathological evaluation, and Masson’s trichrome and Sirius red staining were used for the assessment of renal fibrosis. The mRNA expression of the genes encoding kidney injury molecule-1 (Kim1), vimentin (Vim), α-smooth muscle actin (Acta2), Smad family member 3 (Smad3), and E-cadherin (cdh1), as well as the protein expression of E-cadherin, Kim-1, and connective tissue growth factor (CTGF), was analyzed. Results: LT intervention reduced serum IL-1β and IL-6 levels in the HSD group (P < 0.05). Masson’s trichrome and Sirius red staining showed that glomerular and interstitial fibrosis were significantly reduced in the LT intervention groups (P < 0.05). LT intervention significantly upregulated the mRNA and protein expression of E-cadherin in kidney tissues, which were decreased by HSD (P < 0.05), and downregulated the mRNA expression levels of Vim, Acta2, and Smad3 (P < 0.05). Compared with the HSD group, LT treatment also upregulated E-cadherin protein expression while downregulating α-SMA protein expression (P < 0.05), reduced fibrous tissue accumulation in the renal interstitium, and significantly ameliorated renal fibrosis. Conclusion: L-theanine intervention alleviates high-salt diet-induced renal inflammation and delays the progression of renal fibrosis, and its protective mechanism may be associated with the regulation of E-cadherin, Kim-1, vimentin, and α-SMA expression.

Key words: short-term high-salt exposure; renal injury; L-theanine; renal fibrosis