Diclofenac predisposes benign prostate hyperplasia in fat feed albino rats
Keywords:Diclofenac, Fat, Hepatotoxicity, Haematology, PSA
Background: An attempt to establish the possible cause(s) of benign prostate hyperplasia (BPH) in fat feed albino rats treated with diclofenac (DCF)-potassium (K) was performed to ascertain its likely translational relationship in humans.
Methods: Thirty-five male wistar albino rats of 24 weeks old were divided into five groups of 7 animals each were used. Group 1; the normal control (NC) was injected subcutaneously with the vehicle (olive oil) only and served normal diet. Group 2; standard group treated with testosterone propionate in olive oil (3 mg/kg b. wt.). Groups 3, 4, and 5 were fed with the standard feed mixed with animal fat (sourced from roasted meat/condiments in aluminium foils) in 20, 40 and 80% portions, then treated with DCF-K in solution as low (2 mg/kg b. wt.), mid (4 mg/kg b. wt.), and high (6 mg/kg b. wt.) doses, respectively. The blood samples collected were analysed for prostate specific antigen (PSA), hematological parameters, kidney and liver function.
Results: Group 3 showed the highest PSA elevation (p<0.05) when compared to the control and the untreated group. There was a significant elevation (p<0.05) in WBC levels compared to all other groups. PCV, MCV, NEUT, MONO and EOSIN levels increased significantly (p<0.05) across all groups. Significant (p<0.05) increase was observed in liver and kidney parameters compared to the untreated groups. Significant (p<0.05) elevation in total cholesterol and LDL-C levels across the groups was observed. The DCF-K treated groups showed increase in several parameters compared to the untreated groups.
Conclusions: It was obvious that fatty diet and use of DCF-K contributed to the observed hepatotoxicity, nephrotoxicity, hence predisposed tissue damage and inflammation which conjunctly elevated PSA.
Antoine SG, Carmichael H, Lloyd GL. The Impact of Race, Ethnicity and Insurance Status on Surgery Rates for Benign Prostatic Hyperplasia. Urology. 2021;05:092.
Rundle AG, Sadasivan SM, Chitale DA, Gupta NS, Williamson SR, Kryvenko ON et al. Racial differences in the systemic inflammatory response to prostate cancer. Plos one. 2021;16(7):e0252951.
Gudaru K, Gonzalez Padilla DA, Castellani D, Tortolero Blanco L, Tanidir Y, Ka Lun L et al. A global knowledge, attitudes and practices survey on anatomical endoscopic enucleation of prostate for benign prostatic hyperplasia among urologists. Andrologia. 2020;52(8):e13717.
Mbugua RG, Oluchina S, Karanja. Prostate cancer awareness and screening among men in a rural community in Kenya: a cross-sectional study. Afr J Urol. 2021;27:(7):2-10.
Neimark BD, Tilghman LM. Bioprospecting a biodiversity hotspot: the political economy of natural products drug discovery for conservation goals in Madagascar. In Conservation and environmental management in Madagascar, Routledge. 2014;295-322.
Zaruwa MZ, Muhammad YB, Abdullahi HS, Ubana MA, Ubaoji KI, Adamu RM. Evaluation of Diclofenac (DCF) Potassium as a Possible Predisposer of Benign Prostatic Hyperplasia in Wistar Albino Rats. Saudi J Biomed Res. 2020;8(5):243-8.
Yashin A, Yashin Y, Xia X, Nemzer B. Antioxidant activity of spices and their impact on human health. A review. Antioxidant. 2017;6(3):70:1-18.
Masroor A, Amir RM, Komal F, Nasri MA. Efficacy study of ginger and garlic mixture on hypolidemic and hyperlipidemic parameters of induced diabetic mice. Int J Biosci. 2017;10(1):374-81.
Vidyavati HG, Hanumanthappa M, Hamavathy J, Srinivasan K. Hypolipidemic and antioxidant efficacy of dehydrated onion in experimental rats. J Food Sci Technol. 2010;47(1):55-60.
Mazzone P, Tierney W, Hossain M, Puvenna V, Janigro D, Cucullo L. Pathophysiological impact of cigarette smoke exposure on the cerebrovascular system with a focus on the blood-brain barrier: expanding the awareness of smoking toxicity in an underappreciated area. Int J Environmental Res Public health. 2010;7(12):4111-26.
Biondo PD, Brindley DN, Sawyer MB, Field CJ. The potential for treatment with dietary long-chain polyunsaturated n-3 fatty acids during chemotherapy. J Nutritional Biochem. 2010;19(12):787-96.
Vargas-Sánchez K, Garay-Jaramillo E, González-Reyes RE. Effects of Moringa oleifera on glycaemia and insulin levels: A Review of animal and human studies. Nutrients. 2019;11(12):2907.
Gagliano‐Jucá T, Pencina KM, Guo W, Li Z, Huang G, Basaria S, Bhasin S. Differential effects of testosterone on circulating neutrophils, monocytes, and platelets in men: Findings from two trials. Andrology. 2020;8(5):1324-31.
Aycan İÖ, Elpek Ö, Akkaya B, Kıraç E, Tuzcu H, Kaya S, Aslan M. Diclofenac induced gastrointestinal and renal toxicity is alleviated by thymoquinone treatment. Food Chem Toxicol. 2018;118:795-804.
Parolini M. Toxicity of the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) acetylsalicylic acid, paracetamol, diclofenac, ibuprofen and naproxen towards freshwater invertebrates: A review. Science Total Environment. 2010;740:140043.
Keeley TP, Mann GE. Defining physiological normoxia for improved translation of cell physiology to animal models and humans. Physiological reviews. 2019;99(1):161-234.
Besiroglu H, Dursun M, Otunctemur A, Ozbek E. The association between triglyceride high density lipoprotein cholesterol ratio and benign prostate hyperplasia in non-diabetic patients: a cross-sectional study. Aging Male. 2017;20(3):198-204.
Motawi TK, Ahmed SA, El-Boghdady NA, Metwally NS, Nasr NN. Impact of betanin against paracetamol and diclofenac induced hepato-renal damage in rats. Biomarkers. 2020;25(1):86-93.
Lagathu C, Béréziat V, Gorwood J, Fellahi S, Bastard JP, Vigouroux C et al. Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment. Expert opinion on drug safety. 2019;18(9):829-40.
Sivaraj R, Umarani S. Diclofenac-induced biochemical changes in nephrotoxicity among male Albino rats. Int J Basic Clin Pharmacol. 2018;7:640-3.
Jin R, Strand DW, Forbes CM, Case T, Cates JM, Liu Q et al. The prostaglandin pathway is activated in patients who fail medical therapy for benign prostatic hyperplasia with lower urinary tract symptoms. The Prostate. 2021;81(13):944-55.
Vallina JRP, Cantabrana B, Sanchez M, Hidalgo A. Involvement of sodium/calcium exchange in the diclofenac-induced spasmolytic effect on rat uterus. General pharmacol. 1995;26(6):1249-53.
Sánchez S, De La Lastra CA, Ortiz P, Motilva V, Martín MJ. Gastrointestinal tolerability of metamizol, acetaminophen, and diclofenac in subchronic treatment in rats. Digestive Dis Sci. 2002;47(12):2791-8.
Zeng M, Qi M, Wang Y, Xu R, Wu Y, Li M et al. 5-O-methyldihydroquercetin and cilicicone B isolated from Spina Gleditsiae ameliorate lipopolysaccharide‐induced acute kidney injury in mice by inhibiting inflammation and oxidative stress via the TLR4/MyD88/TRIF/NLRP3 signalling pathway. Int Immunopharmacol. 2020;80:106194.