Effects of Environmentally Relevant Concentrations of Roundup on Oxidative-Nitrative Stress, Cellular Apoptosis, Prooxidant-Antioxidant Homeostasis, Renin and CYP1A Expressions in Goldfish: Molecular Mechanisms Underlying Kidney Damage During Roundup Exposure

Abstract

Roundup is one of the most widely used glyphosate-based harmful herbicides in the United States as well as globally, which poses a severe risk for terrestrial and aquatic organisms. In order to identify the detrimental effects of Roundup exposure in aquatic organisms, we investigated the environmentally relevant concentrations of Roundup exposure (low dose: 0.5 μg/L and high dose: 5.0 μg/L for 2 weeks) on renin expression, oxidative-nitrative stress biomarkers (e.g., 2,4-dinitrophenol, DNP; and 3-nitrotyrosine protein, NTP), prooxidant-antioxidant enzymes expressions (e.g., superoxide dismutase, SOD; and catalase, CAT), cellular apoptosis, and cytochrome P450 1A (CYP1A) mRNA levels in the kidneys of goldfish ( Carassius auratus ). Histopathological and in situ TUNEL analyses showed widespread tissue disruption (e.g., bowman's capsule shrinkage, melanin pigment formation, etc.) and induced apoptotic nuclei in the kidneys of goldfish. Immunohistochemical and quantitative real-time PCR (qRT-PCR) analyses showed a significant (p < 0.05) increase in the expression of renin, DNP, NTP, SOD, and CAT, as well as CYP1A mRNA levels in the kidneys of fish exposed to Roundup. These results suggest that environmentally relevant concentrations of Roundup disrupt kidney architecture by inducing oxidative-nitrative stress, cellular apoptosis, and change in osmoregulatory enzymes (i.e., renin) and prooxidant-antioxidant systems in the kidneys of teleost fishes.