Therapeutic Potential of Pentoxifylline in Paraquat-Induced Pulmonary
                    Toxicity: Role of the Phosphodiesterase Enzymes

Farshad Ghasemi; Mobina Mohammadi; Fatemeh Ghaffari; Ali Hosseini-Sharifabad; Navid Omidifar; Amir Nili-Ahmadabadi

doi:10.1055/a-2314-1137

Drug Research, Table of Contents

Drug Res (Stuttg) 2024; 74(05): 241-249
DOI: 10.1055/a-2314-1137

Original Article

Therapeutic Potential of Pentoxifylline in Paraquat-Induced Pulmonary Toxicity: Role of the Phosphodiesterase Enzymes

Authors

Farshad Ghasemi

¹Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

²Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, North Cyprus, Turkey
Mobina Mohammadi

¹Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

³Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
Fatemeh Ghaffari

¹Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

³Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
Ali Hosseini-Sharifabad

⁴Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
Navid Omidifar

⁵Medical Education Research Center, Department of Pathology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
Amir Nili-Ahmadabadi

¹Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

³Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

Abstract

Pentoxifylline (PTX), a non-selective phosphodiesterase inhibitor, has demonstrated protective effects against lung injury in animal models. Given the significance of pulmonary toxicity resulting from paraquat (PQ) exposure, the present investigation was designed to explore the impact of PTX on PQ-induced pulmonary oxidative impairment in male mice.

Following preliminary studies, thirty-six mice were divided into six groups. Group 1 received normal saline, group 2 received a single dose of PQ (20 mg/kg; i.p.), and group 3 received PTX (100 mg/kg/day; i.p.). Additionally, treatment groups 4–6 were received various doses of PTX (25, 50, and 100 mg/kg/day; respectively) one hour after a single dose of PQ. After 72 hours, the animals were sacrificed, and lung tissue was collected.

PQ administration caused a significant decrease in hematocrit and an increase in blood potassium levels. Moreover, a notable increase was found in the lipid peroxidation (LPO), nitric oxide (NO), and myeloperoxidase (MPO) levels, along with a notable decrease in total thiol (TTM) and total antioxidant capacity (TAC) contents, catalase (CAT) and superoxide dismutase (SOD) enzymes activity in lung tissue. PTX demonstrated the ability to improve hematocrit levels; enhance SOD activity and TTM content; and decrease MPO activity, LPO and NO levels in PQ-induced pulmonary toxicity. Furthermore, these findings were well-correlated with the observed lung histopathological changes.

In conclusion, our results suggest that the high dose of PTX may ameliorate lung injury by improving the oxidant/antioxidant balance in animals exposed to PQ.

Keywords

pentoxifylline - paraquat - lung toxicity - oxidative stress

Full Text

References

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