Meloxicam Alleviates Oxidative Stress Through Nrf2/HO-1 Activation in Bovine Endometrial Epithelial Cells

TL;DR

Meloxicam reduces oxidative stress in bovine endometrial cells by activating the Nrf2/HO-1 pathway, offering a potential treatment for uterine diseases in cows.

Contribution

This study identifies the Nrf2/HO-1 pathway as the key mechanism through which meloxicam exerts its antioxidant effects in bovine endometrial cells.

Findings

Meloxicam activates the Nrf2/HO-1 pathway to reduce oxidative stress in bovine endometrial epithelial cells.

Meloxicam is more effective than NAC in promoting Nrf2 pathway activation and antioxidant enzyme activity.

Inhibiting Nrf2 or HO-1 reduces meloxicam's antioxidant effects, confirming the pathway's role.

Abstract

Oxidative stress in cattle can lead to uterine diseases. Meloxicam possesses anti-inflammatory and antioxidant properties and plays a crucial role in the adjuvant treatment of uterine diseases in dairy cows. This research explored how meloxicam influences oxidative stress responses and their underlying mechanisms in the epithelial cells of the bovine endometrium. We found that meloxicam protected cells from oxidative stress by activating the Nrf2/HO-1antioxidant pathway. This research contributes to elucidating the mechanism underlying meloxicam’s therapeutic action in the bovine endometrium.

Meloxicam has been identified as an adjuvant therapeutic component in the management of bovine uterine diseases, exhibiting anti-inflammatory and antioxidant effects. However, the mechanisms underlying its antioxidant actions in the context of bovine uterine diseases remain incompletely understood. The objective of this research was to determine whether meloxicam exerts its antioxidant effects through the Nrf2/HO-1 signaling pathway. By employing N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS), along with inhibitors directed against heme oxygenase-1 (HO-1) or nuclear factor erythroid 2-related factor 2 (Nrf2), we investigated the dynamic changes in oxidative stress markers (ROS and malondialdehyde) and antioxidant indices (comprising catalase, superoxide dismutase, and glutathione), as well as the expression profiles of Nrf2 and inflammation-associated genes and proteins in bovine endometrial epithelial cells (BEECs) subjected to lipopolysaccharide (LPS) stimulation. As a result, meloxicam alleviated the LPS-induced elevation of oxidative stress marker levels and the reduction in antioxidant enzyme activities and antioxidant substance contents in BEECs. Compared to NAC, meloxicam demonstrated superior efficacy in activating the Nrf2 pathway, with the promotion of NRF2 expression (~1.6-fold) and nuclear translocation. The pretreatment of cells with HO-1 or Nrf2 inhibitors markedly attenuated the antioxidant activity of meloxicam. In summary, meloxicam primarily alleviates LPS-induced oxidative stress through the activation of the Nrf2/HO-1 pathway in BEECs.

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