Ivermectin ameliorates bleomycin-induced lung fibrosis in male rats by inhibiting the inflammation and oxidative stress

Abstract

Background

Idiopathic pulmonary fibrosis (IPF) is a pulmonary fibrotic disease characterized by a poor prognosis, which its pathogenesis involves the accumulation of abnormal fibrous tissue, inflammation, and oxidative stress. Ivermectin, a positive allosteric modulator of GABA_A receptor, exerts anti-inflammatory and antioxidant properties in preclinical studies. The present study investigates the potential protective effects of ivermectin treatment in rats against bleomycin-induced IPF.

Materials and Methods

The present study involved 42 male Wistar rats, which were divided into five groups: control (without induction of IPF), bleomycin (IPF-induced by bleomycin 2.5 mg/kg, by intratracheal administration), and three fibrosis groups receiving ivermectin (0.5, 1, and 3 mg/kg). lung tissues were harvested for measurement of oxidative stress [via myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione (GSH)] and inflammatory markers (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], and transforming growth factor-β [TGF-β]). Histological assessments of tissue damage were performed using hematoxylin–eosin (H&E) and Masson’s trichrome staining methods.

Results

The induction of fibrosis via bleomycin was found to increase levels of MPO as well as TNF-α, IL-1β, and TGF-β while decrease SOD activity and GSH level. Treatment with ivermectin at a dosage of 3 mg/kg was able to reverse the effects of bleomycin-induced fibrosis on these markers. In addition, results from H&E and Masson’s trichrome staining showed that ivermectin treatment at this same dose reduced tissue damage and pulmonary fibrosis.

Conclusion

The data obtained from this study indicate that ivermectin may have therapeutic benefits for IPF, likely due to its ability to reduce inflammation and mitigate oxidative stress-induced toxicity.

Keywords:

• Pulmonary fibrosis
• bleomycin
• inflammation
• oxidative stress
• ivermectin
• rat

Acknowledgments

This work was supported by a grant from Experimental Medicine Research Center, Tehran University of Medical Sciences (Grant No. 9811299005-54444). Special thanks to Iran National Science Foundation (INSF) for their support.

Ethics approval and consent to participate

All experimental steps were performed according to the authorized instructions of animal care and ethics of Tehran University of Medical Sciences (IR.TUMS.AEC.1401.004).

Disclosure statement

The author declares that there are no conflicts of interest that could influence or bias the content of this work. There was no financial or personal relationship with other individuals or organizations that could inappropriately influence or bias the content of this work.

Data availability statement

The data of the present study are available from the corresponding author on reasonable request.