Insight Into the Mechanisms of Aquatic Heavy Metal Intoxication in Modulating Programmed Cell Death Pathways in Fish: Paradigms From Cellular to Ecosystem Scale

ABSTRACT Heavy metals are prevalent environmental contaminants owing to their persistence and non‐biodegradability, making their elimination extremely challenging. Heavy metal pollutants in aquatic ecosystems result in numerous detrimental consequences on aquatic animals, particularly fish. Fish is an essential and economical source of nutrients, abundant in minerals and proteins. Exposure of fish to heavy metals generates reactive oxygen species, leading to oxidative stress and inflammation, and thereby compromising fish development and health. The accumulation of heavy metals in aquatic ecosystems can be transferred to human tissues through the consumption of contaminated fish, potentially leading to significant health consequences. Programmed cell death (PCD) is a tightly regulated process of cellular death that maintains homeostasis and facilitates developmental processes. It is crucial in the pathogenic mechanisms of heavy metal‐induced toxicity. Identifying pivotal molecules and understanding their regulation mechanisms are crucial for improved disease prevention and management. This literature review seeks to elucidate and elaborate on the rapidly evolving functions of diverse PCD mechanisms, such as apoptosis, autophagy, pyroptosis, ferroptosis, cuproptosis, oxeiptosis, necroptosis, and cuPANoptosis, in the development and progression of heavy metal‐induced toxicity in fish.