Matricin Modulates Carbamazepine-Induced Acute Tubulointerstitial Nephritis in Rat Models of Alzheimer's Disease via MEK-JAK2-STAT3 Signaling

Carbamazepine is a first-choice anticonvulsant, and its medication is typically well tolerated when compared to lithium and valproic acid. Patients of Alzheimer's Disease who are administered carbamazepine tend to develop acute tubulointerstitial nephritis. In this study, we established an Alzheimer's model using scopolamine in Sprague Dawley rats to find out the nephroprotective effect of matricin (a bioactive sesquiterpene isolated from chamomile flowers) against carbamazepine-induced acute tubulointerstitial nephritis and its underlying mechanism of action. Scopolamine (16 mg/kg) was intraperitoneally injected for induction of Alzheimer's disease on the 28th day whereas carbamazepine (25 mg/kg) was given daily to induce acute tubulointerstitial nephritis. Treatment with matricin inhibited carbamazepine-induced mRNA expressions of RAS-ERK-MEK-JAK2-STAT3, cytokines (IL-1 beta, TNF-alpha, and IL-6), and restored the optimal levels of biomarkers of oxidative stress (MDA, SOD and CAT). Further, matricin treatments reinstated biomarkers of kidney function (creatinine, uric acid, and blood urea nitrogen), and refurbished the levels of MDA, SOD, and CAT. Histopathological analyses indicated that there was systemic dilation, tubular necrosis, interstitial edema, and glomerulus nephritis in the medulla region of the kidneys in rats with Alzheimer's disease that received carbamazepine only. Treatment with matricin reconsolidated histopathology, and only mild glomerulus nephritis were observed in rats with Alzheimer's disease. These results suggest that matricin could be utilized as a co-supplement with carbamazepine for the treatment of patients with Alzheimer's disease to minimize the risk of kidney damage.