Light and heavy ferritin chain expression in the liver and kidneys of Wistar rats: aging, sex differences, and impact of gonadectomy

Abstract

Ferritin is the main intracellular storage of iron. Animal studies show that female liver and kidney express more ferritin and accumulate more iron than male. However, no study so far has investigated sex and age differences in light (FtL) and heavy (FtH) ferritin chain expression. To address this, we relied on specific antibodies and immunochemical methods to analyse the expression of both ferritin chains in the liver and kidney of 3-month and 2-year-old male and female Wistar rats. To see how sex hormones may affect expression we also studied adult animals gonadectomised at the age of 10 weeks. FtL and FtH were more expressed in both organs of female rats, while gonadectomy increased the expression in males and decreased it in females, which suggests that it is stimulated by female and inhibited by male steroid hormones. Normal kidney ferritin distribution and change with aging warrant more attention in studies of (patho) physiological and toxicological processes.

Differences in hepatocellular iron metabolism underlie sexual dimorphism in hepatocyte ferroptosis

“…We have recently shown that iron-loaded hepatocytes undergo ferroptosis because of iron-catalyzed overproduction of mitochondrial reactive oxygen species (mtROS) [ 32 ]. Intriguingly, sexual dimorphism in iron metabolism has been well noted in humans and in experimental rodents [ [33] , [34] , [35] ]. Hepatocytes, which compromise approximately 80% of the liver mass, play an important role in systemic iron homeostasis via the deposition of excessive body iron and production of hepcidin [ 36 ], a master regulator of iron metabolism.…”

Differences in Hepatocellular Iron Metabolism Underlie Sexual Dimorphism in Hepatocyte Ferroptosis

“…We have recently shown that iron-loaded hepatocytes undergo ferroptosis because of iron-catalyzed overproduction of mitochondrial reactive oxygen species (mtROS) [18]. Intriguingly, sexual dimorphism in iron metabolism has been well noted in humans and in experimental rodents [19][20][21]. Hepatocytes, which compromise approximately 80% of the liver mass, play an important role in systemic iron homeostasis via the deposition of excessive body iron and production of hepcidin [22], a master regulator of iron metabolism.…”

Sex difference in the association between blood alcohol concentration and serum ferritin

“…Indeed, one study showed sex-specific association between brain iron content and cognitive decline in aging-related iron disturbance (32). In a study of healthy individuals (93 males and 72 females), there was a significant increase in brain ferritin iron in the basal ganglia and hippocampus associated with aging, however women showed much lower brain ferritin than men (33). Interestingly, the kidney and liver of aging female rats showed higher expression of ferritin than in males (34).…”