Capsaicin Decreases Kidney Iron Deposits and Increases Hepcidin Levels in Diabetic Rats with Iron Overload: A Preliminary Study

Abstract

Iron overload (IOL) increases the risk of diabetes mellitus (DM). Capsaicin (CAP), an agonist of transient receptor potential vanilloid-1 (TRPV1), reduces the effects of IOL. We evaluated the effects of chronic CAP administration on hepcidin expression, kidney iron deposits, and urinary biomarkers in a male Wistar rat model with IOL and DM (DM-IOL). IOL was induced with oral administration of iron for 12 weeks and DM was induced with streptozotocin. Four groups were studied: Healthy, DM, DM-IOL, and DM-IOL + CAP (1 mg·kg−1·day−1 for 12 weeks). Iron deposits were visualized with Perls tissue staining and a colorimetric assay. Serum hepcidin levels were measured with an enzyme-linked immunosorbent assay. Kidney biomarkers were assayed in 24 h urine samples. In the DM-IOL + CAP group, the total area of iron deposits and the total iron content in kidneys were smaller than those observed in both untreated DM groups. CAP administration significantly increased hepcidin levels in the DM-IOL group. Urinary levels of albumin, cystatin C, and beta-2-microglobulin were similar in all three experimental groups. In conclusion, we showed that in a DM-IOL animal model, CAP reduced renal iron deposits and increased the level of circulating hepcidin.

Nutritional Modulation of Hepcidin in the Treatment of Various Anemic States

“…On the contrary, the consumption of chili pepper, whose main important component is capsaicin, may not be indicated in patients with anemia with increased hepcidin. In this context, one recent study reported that the chronic administration of capsaicin for 12 weeks increased hepcidin levels in the serum of diabetic mice [101].…”

Spice Up Your Kidney: A Review on the Effects of Capsaicin in Renal Physiology and Disease

“…Iron overload, which is common in diabetes, may trigger or worsen DKD [65]. In an interesting experiment, chronic capsaicin administration was tested in male Wistar rats with iron overload (IOL) and diabetes mellitus + IOL [66]. Capsaicin markedly reduced kidney iron deposits by increasing the circulating levels of hepcidin, an important regulator of iron homeostasis, but had apparently no relevant effects on biomarkers of renal damage such as albuminuria, cystatin C, and beta-2-microglobulin.…”

Capsaicin alleviates doxorubicin-induced acute myocardial injury by regulating iron homeostasis and PI3K-Akt signaling pathway

“…Another particular note is its influence on the pivotal PI3K-Akt pathway. Studies have unveiled that CAP can modulate the PI3K-Akt pathway at multiple tiers [ 21 , 24 ]. It can stimulate PI3K activity, initiating the phosphorylation and activation of Akt, which subsequently orchestrates downstream events associated with cell proliferation and survival.…”

“…Recent investigations have unveiled its antioxidative, anti-inflammatory, and anticancer attributes [16][17][18][19][20]. Notably, CAP has been found to influence cellular iron metabolism, potentially impacting iron-dependent processes [21]. Specifically, CAP has ability of inhibition ferroptosis in normal tissue to protect it, it regulates ferroptosis through combination with iron, but it also could induce cancer ferroptosis through regulation SLC7A11-GPX4 signaling pathway [22,23].…”