Diosmin ameliorative effects on oxidative stress and fibrosis in paraquat-induced lung injury in mice
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Paraquat (PQ) induces pulmonary fibrosis, a progressive lung disorder resulting in severe respiratory failure and death. Increased oxidative stress, inflammatory reactions, and multiple fibrotic lesions are major features of PQ-induced lung injury. Diosmin (Dio) is a safe drug that is available for clinical use for vascular disorders. Dio exhibits antioxidant, anti-inflammatory, and antifibrotic activities. Accordingly, the aim of this study was to evaluate the protective effect of diosmin on PQ-induced lung injury in mice and the underlying mechanisms involved. Lung injury was induced by PQ (30 mg/kg, intraperitoneally) in NMRI albino mice and Dio (50 and 100 mg/kg, gavage) was administrated 3 days before PQ and continued for 10 or 24 days. After euthanizing the mice, the biochemical and histopathological markers of lung tissue were determined. PQ significantly increased oxidative stress, inflammatory, and fibrotic markers. PQ increased the level of malonedaldehyde (MDA) and hydroxyproline (HYP) and decreased the level of glutathione (GSH) and catalase activity in the lung. Dio (50 and 100 mg/kg) significantly increased GSH levels and catalase activity and decreased HYP content and MDA levels. In addition, Dio reduced histopathological injuries in hematoxylin and eosin–stained and Masson’s trichrome–stained sections. These findings suggest that Dio has protective effects against PQ-induced lung injury, which may be due to its antioxidant, anti-inflammatory, and antifibrotic effects.
KeywordsParaquat Pulmonary injury Diosmin Antioxidant Antifibrotic Mice
This paper is issued from the Pharm.D thesis of Sirus Mirzaee and was financially supported by the Toxicology Research Center (Grant Number: TRC-9607) of AJUMS.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
- Autor A (1977) Biochemical mechanisms of paraquat toxicity. Academic Press Inc, New YorkGoogle Scholar
- Buddhan R, Manoharan S (2017) Diosmin reduces cell viability of A431 skin cancer cells through apoptotic induction. J Cancer Res Ther 13(3):471–476Google Scholar
- Heusser J, Osswald W (1977) Toxicological properties of diosmin and its actions on the isolated venous tissue of the dog. Arch Farmacol Toxicol 3:33–40Google Scholar
- Imam F, Al-Harbi NO, Al-Harbi MM, Ansari MA, Zoheir KM, Iqbal M, Anwer MK, Al Hoshani AR, Attia SM, Ahmad SF (2015) Diosmin downregulates the expression of T cell receptors, pro-inflammatory cytokines and NF-kappaB activation against LPS-induced acute lung injury in mice. Pharmacol Res 102:1–11CrossRefGoogle Scholar
- Kumar VCR, Rabbins SL (1997) Basic pathology. W.B. Saunders Company, Philadelphia, p 52Google Scholar
- Ruscitti F, Ravanetti F, Essers J, Ridwan Y, Belenkov S, Vos W, Ferreira F, KleinJan A, van Heijningen P, Van Holsbeke C, Cacchioli A, Villetti G, Stellari FF (2017) Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice. Multidiscip Respir Med 12:8CrossRefGoogle Scholar
- Sabzghabaee A, Eizadi-Mood N, Montazeri K, Yaraghi A, Golabi M (2010) Fatality in paraquat poisoning. Singapore Med J 51:496–500Google Scholar
- Szapiel SV, Elson NA, Fulmer JD, Hunninghake GW, Crystal RG (1979): Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis 120, 893-9Google Scholar
- Tahir M, Rehman MU, Lateef A, Khan AQ, Khan R, Qamar W, O’Hamiza O, Ali F, Hasan SK, Sultana S (2013) Diosmin abrogates chemically induced hepatocarcinogenesis via alleviation of oxidative stress, hyperproliferative and inflammatory markers in murine model. Toxicol Lett 220:205–218CrossRefGoogle Scholar
- Wang Y, Zhou M, Lu Y, Yu A, Li J (2017) Protective effect of 5-aminosalicylic acid on the kidney of paraquat poisoning rats by Nrf2-ARE signal pathway. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 29:961–966Google Scholar
- Xu S, Hu H, Jiang Z, Tang S, Zhou Y, Sheng J, Chen J, Cao Y (2015) APACHE score, Severity Index of Paraquat Poisoning, and serum lactic acid concentration in the prognosis of paraquat poisoning of Chinese Patients. Pediatr Emerg Care 31:117–121Google Scholar