Atrazine Triggers the Extrinsic Apoptosis Pathway in Lymphocytes of the Frog Pelophylax nigromaculata in Vivo.

Abstract

Atrazine (ATR) is extensively used worldwide as an herbicide, with a global ecological influence. The widespread distribution of herbicides may be one of the possible reasons for the decline in the global amphibian population. The acute toxicity and potential toxicological mechanisms of ATR on the immune system of frogs are not well-understood. In this study, Pelophylax nigromaculata was used as an experimental carrier and exposed to 0, 1, 10, 100, and 1000 μg/L ATR solutions for 14 days, resulting in a significant decrease in the viability of their lymphocytes. The characteristics of apoptosis, such as DNA damage, percentage of apoptotic cells, DNA laddering, and morphological features, were measured in lymphocytes from the ATR-exposed groups, and the increase in apoptosis observed appears to be the result of the alterated expression of some key proteins in the extrinsic apoptosis pathway. The expression of the key apoptosis proteins Fas, Fas-L, c-FLIP, caspase-8, Bid, and caspase-3 was significantly modulated in a dose-dependent manner. Moreover, c-FLIP was shown to modulate the Fas-dependent apoptosis of the lymphocytes. In summary, acute ATR exposure damaged the lymphocytes, resulting in their apoptosis via an extrinsic signaling pathway. This study provides novel insights into the immunological and toxicological responses of amphibians exposed to triazine herbicides.