Apigenin Ameliorates Genitourinary Dysfunction in a Type 1 Diabetic Rat Model Via Drp1 Modulation

Overview

Journal Sci Rep

Specialty Science

Date 2024 Mar 8

PMID 38459102

Authors

Mai Khaled

Raghda A M Salama

Azza Aboughalia

Mai Tarek

Nesma Mohamed Fawzy

Affiliations

Soon will be listed here.

Abstract

The present study aimed to explore the potential ameliorative effect of apigenin (APG) against diabetes-associated genitourinary complications in rats. A diabetic rat model was induced by the intraperitoneal injection of streptozotocin (STZ). All experimental animals were treated with vehicle or vehicle plus APG at a dose of 0.78 mg/kg/day for 10 days, either once diabetes was confirmed or at the end of the 3rd week after confirmation of diabetes. Rats were sacrificed at the end of the fifth week. In addition to the histological assessment, an analysis of kidney function tests and serum testosterone was performed to assess diabetic genitourinary complications. Gene expression of the mitochondrial fission protein, dynamin related protein 1 (Drp1), was measured in renal and testicular tissues using qRT PCR. APG can increase body weight, reduce blood glucose levels, and improve renal and testicular functions in diabetic rats. APG decreased Drp1 overexpression in diabetic animals' kidneys and testes. In summary, our current work discloses that APG attenuates diabetic genitourinary lesions in rats via suppressing Drp1 overexpression.

Citing Articles

The effect of hydrophilic statins on adiponectin, leptin, visfatin, and vaspin levels in streptozocin-induced diabetic rats.

Kaya H, Demirtas B Naunyn Schmiedebergs Arch Pharmacol. 2024; .

PMID: 39382680 DOI: 10.1007/s00210-024-03517-6.

COVID-19-Associated Sepsis: Potential Role of Phytochemicals as Functional Foods and Nutraceuticals.

De Souza Goncalves B, Sangani D, Nayyar A, Puri R, Irtiza M, Nayyar A Int J Mol Sci. 2024; 25(15).

PMID: 39126050 PMC: 11312872. DOI: 10.3390/ijms25158481.

References

Huang S, Wang Y, Gan X, Fang D, Zhong C, Wu L . Drp1-mediated mitochondrial abnormalities link to synaptic injury in diabetes model. Diabetes. 2014; 64(5):1728-42. PMC: 4407851. DOI: 10.2337/db14-0758. View

Hou Y, Zhang Y, Lin S, Yu Y, Yang L, Li L . Protective mechanism of apigenin in diabetic nephropathy is related to its regulation of miR-423-5P-USF2 axis. Am J Transl Res. 2021; 13(4):2006-2020. PMC: 8129299. View

Song S, Park J, Jang S, Hwang E . Nicotinamide Treatment Facilitates Mitochondrial Fission through Drp1 Activation Mediated by SIRT1-Induced Changes in Cellular Levels of cAMP and Ca. Cells. 2021; 10(3). PMC: 7999186. DOI: 10.3390/cells10030612. View

Nekoua M, Alidjinou E, Hober D . Persistent coxsackievirus B infection and pathogenesis of type 1 diabetes mellitus. Nat Rev Endocrinol. 2022; 18(8):503-516. PMC: 9157043. DOI: 10.1038/s41574-022-00688-1. View

Fang D, Wan X, Deng W, Guan H, Ke W, Xiao H . Fufang Xue Shuan Tong capsules inhibit renal oxidative stress markers and indices of nephropathy in diabetic rats. Exp Ther Med. 2012; 4(5):871-876. PMC: 3493747. DOI: 10.3892/etm.2012.680. View

Panda S, Kar A . Apigenin (4',5,7-trihydroxyflavone) regulates hyperglycaemia, thyroid dysfunction and lipid peroxidation in alloxan-induced diabetic mice. J Pharm Pharmacol. 2007; 59(11):1543-8. DOI: 10.1211/jpp.59.11.0012. View

Malik S, Suchal K, Irfan Khan S, Bhatia J, Kishore K, Dinda A . Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways. Am J Physiol Renal Physiol. 2017; 313(2):F414-F422. DOI: 10.1152/ajprenal.00393.2016. View

Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey M, Baker M . The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 2020; 18(7):e3000410. PMC: 7360023. DOI: 10.1371/journal.pbio.3000410. View

Men X, Wang H, Li M, Cai H, Xu S, Zhang W . Dynamin-related protein 1 mediates high glucose induced pancreatic beta cell apoptosis. Int J Biochem Cell Biol. 2008; 41(4):879-90. DOI: 10.1016/j.biocel.2008.08.031. View

10.

Li J, Wang Y, Wu T, Li S, Sun Y, Liu Z . Baicalein suppresses high glucose-induced inflammation and apoptosis in trophoblasts by targeting the miRNA-17-5p-Mfn1/2-NF-κB pathway. Placenta. 2022; 121:126-136. DOI: 10.1016/j.placenta.2022.02.013. View

11.

Skondras I, Lambropoulou M, Tsaroucha A, Gardikis S, Tripsianis G, Simopoulos C . The role of Apigenin in testicular damage in experimental ischemia-reperfusion injury in rats. Hippokratia. 2016; 19(3):225-30. PMC: 4938469. View

12.

Tagaya M, Kume S, Yasuda-Yamahara M, Kuwagata S, Yamahara K, Takeda N . Inhibition of mitochondrial fission protects podocytes from albumin-induced cell damage in diabetic kidney disease. Biochim Biophys Acta Mol Basis Dis. 2022; 1868(5):166368. DOI: 10.1016/j.bbadis.2022.166368. View

13.

Vincent A, Edwards J, McLean L, Hong Y, Cerri F, Lopez I . Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy. Acta Neuropathol. 2010; 120(4):477-89. PMC: 4254759. DOI: 10.1007/s00401-010-0697-7. View

14.

Shi Y, Bai J, Dang Y, Bai Q, Zheng R, Chen J . Protection of apigenin against acrylonitrile-induced sperm and testis injury in rats: involvement of activation of ASK1-JNK/p38 signaling pathway. Toxicol Res (Camb). 2021; 10(2):159-168. PMC: 8045582. DOI: 10.1093/toxres/tfab017. View

15.

Xu K, Yang Y, Lan M, Wang J, Liu B, Yan M . Apigenin alleviates oxidative stress-induced myocardial injury by regulating SIRT1 signaling pathway. Eur J Pharmacol. 2023; 944:175584. DOI: 10.1016/j.ejphar.2023.175584. View

16.

Che D, Cho B, Kim J, Shin J, Kang H, Jang S . Luteolin and Apigenin Attenuate LPS-Induced Astrocyte Activation and Cytokine Production by Targeting MAPK, STAT3, and NF-κB Signaling Pathways. Inflammation. 2020; 43(5):1716-1728. DOI: 10.1007/s10753-020-01245-6. View

17.

Qi C, Mao X, Zhang Z, Wu H . Classification and Differential Diagnosis of Diabetic Nephropathy. J Diabetes Res. 2017; 2017:8637138. PMC: 5337846. DOI: 10.1155/2017/8637138. View

18.

Altara R, Zouein F, Booz G . Untangling the Interplay Between Mitochondrial Fission and NF-κB Signaling in Endothelial Inflammation. Hypertension. 2020; 76(1):23-25. DOI: 10.1161/HYPERTENSIONAHA.120.14854. View

19.

Zhang M, Zhu L, Zheng X, Xie T, Wang W, Zou J . TGR5 Activation Ameliorates Mitochondrial Homeostasis Regulating the PKCδ/Drp1-HK2 Signaling in Diabetic Retinopathy. Front Cell Dev Biol. 2022; 9:759421. PMC: 8795816. DOI: 10.3389/fcell.2021.759421. View

20.

Wang P, Zhang S, Lin S, Lv Z . Melatonin ameliorates diabetic hyperglycaemia-induced impairment of Leydig cell steroidogenic function through activation of SIRT1 pathway. Reprod Biol Endocrinol. 2022; 20(1):117. PMC: 9373359. DOI: 10.1186/s12958-022-00991-6. View