Abstract:
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 tubuloin-
terstitial 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 carbam-
azepine-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-1β, TNF-α, and IL-6), and restored the optimal levels of
biomarkers of oxidative stress (MDA, SOD and CAT). Further, matricin treatments reinstated biomarkers of kidney func-
tion (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