Damir SULJEVIC, Asija ZAČIRAGIĆ, Višnja MUZIKA, Amina VALJEVAC, Amela DERVIŠEVIĆ, Maja MITRASINOVIC-BRULIC, Muhamed FOČAK, Esad ĆOSOVIĆ, Selma ALIČELEBIC, Samra ČUSTOVIC

The protective effects of vitamin D3 on histopathology of pancreas and liver in streptozotocin-induced diabetic rats

The purpose of this study was to explore possible protective effects of vitamin D3 on serum glucose concentration, body weight and histopathology of pancreas and liver. Animals were divided into 3 groups: Control group (n=6), streptozotocin (STZ) group (n=6) and streptozotocin + vitamin D3 (STZ+D3) group (n=6). Rats in the STZ+D3 group starting from the 7th day of experiment were given vitamin D3 for 14 days. Glucose levels and body weight were measured on the 1, 7, 14 and 21st day of experiment. Qualitative histological analysis of pancreas and liver was done using the light microscope with a digital camera. Differences between the groups were tested by one-way analysis of variance (ANOVA) followed by Dunnett's posttest. Differences in repeated measures were tested using paired t-test. On day 14 and 21, blood glucose level in STZ+D3 group was significantly higher compared to the control group of animals but significantly lower than the glucose level registered in STZ group of rats. On day 14 and day 21, body weight in STZ rats was significantly lower compared to weight in STZ+D3 and control groups of rats. Morphological changes, such as shrinkage of islets, vacuolation of both endocrine and exocrine cells, were observed in pancreas of STZ group of animals but were nearly absent in STZ+D3 rats. Similarly, STZ+D3 group of rats showed preserved liver histoarchitecture. Obtained results suggest that vitamin D3 treatment reduces hyperglycemia, exerts beneficial effects on body weight and alleviates histopathological changes in pancreas and liver in STZ-induced diabetic rats.

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[1] Lu L, Lu Q, Chen W, Li J, Li C, Zheng Z. Vitamin D3 protects against diabetic retinopathy by inhibiting high-glucoseinduced activation of the ROS/TXNIP/NLRP3 inflammasome pathway. J Diabetes Res. 2018; 8193523. [CrossRef]
[2] George N, Kumar TP, Antony S, Jayanarayanan S, Paulose CS. Effect of vitamin D3 in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats. Br J Nutr. 2012; 108 (8): 1410‐1418. [CrossRef]
[3] Mitrašinović-Brulić M, Dervišević A, Začiragić A, Fočak M, Valjevac A, Hadžović-Džuvo A, Suljević D. Vitamin D3 attenuates oxidative stress and regulates glucose level and leukocyte count in a semi-chronic streptozotocin-induced diabetes model. J Diabetes Metab Disord. 2021; 20 (1): 771-779. [CrossRef]
[4] Zafar M, Naeem-Ul-Hasan Naqui S. Effects of STZ-induced diabetes on the relative weights of kidney, liver and pancreas in albino rats: a comparative study. Int J Morphol. 2010; 28 (1): 135-142. [CrossRef]
[5] Plum LA, DeLuca HF. Vitamin D, disease and therapeutic opportunities. Nat Rev Drug Discov. 2010; 9 (12): 941‐ 955. [CrossRef]
[6] Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013; 5 (7): 2502‐2521.[CrossRef]
[7] Chagas CE, Borges MC, Martini LA, Rogero MM. Focus on vitamin D, inflammation and type 2 diabetes. Nutrients. 2012; 4 (1): 52‐67. [CrossRef]
[8] Guillot X, Semerano L, Saidenberg-Kermanac'h N, Falgarone G, Boissier MC. Vitamin D and inflammation. Joint Bone Spine. 2010; 77 (6): 552‐557. [CrossRef]
[9] Tarcin O, Yavuz DG, Ozben B, Telli A, Velioglu Ogunc A, Yuksel M, Toprak A, Yazici D, Sancak S, Deyneli O, Akalin S. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab. 2009; 94 (10): 4023‐4030. [CrossRef]
[10] Payne JF, Ray R, Watson DG, Delille C, Rimler E, Cleveland J, Lynn MJ, Tangpricha V, Srivastava SK. Vitamin D insufficiency in diabetic retinopathy. Endocr Pract. 2012; 18 (2): 185‐193. [CrossRef]
[11] Hyppönen E, Läärä E, Reunanen A, Järvelin M-R, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birthcohort study. Lancet. 2001; 358: 1500-1503. [CrossRef]
[12] Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007; 92 (6): 2017‐2029. [CrossRef]
[13] Kumar PT, Antony S, Nandhu MS, Sadanandan J, Naijil G, Paulose CS. Vitamin D3 restores altered cholinergic and insulin receptor expression in the cerebral cortex and muscarinic M3 receptor expression in pancreatic islets of streptozotocin induced diabetic rats. J Nutr Biochem. 2011; 22 (5): 418‐425. [CrossRef]
[14] Derakhshanian H, Djalali M, Mohammad Hassan MH, Alvandi E, Eshraghianet MR, Mirshafiey A, Nadimi H, Jahanabadi S, Zarei M, Djazayery A. Vitamin D suppresses cellular pathways of diabetes complication in liver. Iran J Basic Med Sci. 2019; 22 (6): 690‐694. [CrossRef]
[15] Kaur H, Donaghue KC, Chan AK, Benitez-Aguirre P, Hing S, Lloyd M, Cusumano J, Pryke A, Craig ME. Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1 diabetes. Diabetes Care. 2011; 34 (6): 1400‐1402. [CrossRef]
[16] Diaz VA, Mainous AG, Carek PJ, Wessell AM, Everett CJ. The association of vitamin D deficiency and insufficiency with diabetic nephropathy: implications for health disparities. J Am Board Fam Med. 2009; 22 (5): 521‐527. [CrossRef]
[17] Hussein AG, Mohamed RH, Shalaby SM, Abd El Motteleb DM. Vitamin K2 alleviates type 2 diabetes in rats by induction of osteocalcin gene expression. Nutrition. 2018; 47: 33‐38. [CrossRef]
[18] Kocaman N, Kuloğlu T. Expression of asprosin in rat hepatic, renal, heart, gastric, testicular and brain tissues and its changes in a streptozotocin-induced diabetes mellitus model. Tissue Cell. 2020; 66: 101397. [CrossRef]
[19] Alatawi FS, Faridi UA, AlatawiMS. Effect of treatment with vitamin D plus calcium on oxidative stress in streptozotocin-induced diabetic rats. Saudi Pharm J. 2018; 26 (8): 1208-1213. [CrossRef]
[20] Liu L, Lv G, Ning C, Yang YE, Zhu J. Therapeutic effects of 1,25-dihydroxyvitamin D3 on diabetes-induced liver complications in a rat model. Exp Ther Med. 2016; 11 (6): 2284-2292. [CrossRef]
[21] Hamden K, Carreau S, Jamoussi K, Miladi S, Lajmi S, Aloulou D, Ayadi F, Elfeki A.1 Alpha, 25 dihydroxyvitamin D3: therapeutic and preventive effects against oxidative stress, hepatic, pancreatic and renal injury in alloxan-induced diabetes in rats. J Nutr Sci Vitaminol. 2009; 55 (3): 215-222. [CrossRef]
22] Omidian M, Djalali M, Javanbakht MH, Eshraghian MR, Abshirini A, Omidian P, Alvandi E, Mahmoudi M. Effects of vitamin D supplementation on advanced glycation end products signaling pathway in T2DM patients: a randomized, placebo-controlled, double blind clinical trial. Diabetol Metab Syndr. 2019; 11: 86. [CrossRef]
[23] Mitri J, Pittas AG. Vitamin D and diabetes. Endocrinol Metab Clin North Am. 2014; 43 (1): 205-232. [CrossRef]
[24] Neelankal John A, Jiang FX. An overview of type 2 diabetes and importance of vitamin D3-vitamin D receptor interaction in pancreatic β-cells. J Diabetes Complications. 2018; 32 (4): 429‐443. [CrossRef]
[25] Lee HA, Lee E, Do GY, Moon EK, Quan FS, Kim I. Histone deacetylase inhibitor MGCD0103 protects the pancreas from streptozotocin-induced oxidative stress and β-cell death. Biomed Pharmacother. 2019; 109: 921-929. [CrossRef]
[26] Furman BL. Streptozotocin-induced diabetic models in mice and rats. Curr Protoc Pharmacol. 2015; 70: 5471-54720. [CrossRef]
[27] Wang Y, He D, Ni C, Zhou H, Wu S, Xue Z, Zhpu Z. Vitamin D induces autophagy of pancreatic β-cells and enhances insulin secretion. Mol Med Rep. 2016; 14 (3): 2644-2650. [CrossRef]
[28] Zmijewski MA. Vitamin D and human health. Int J Mol Sci. 2019; 20 (1):145. [CrossRef]
[29] Megahed A, Gadalla H, Abdelhamid F, Fawzy M, Risha E. Protective effects of Vitamin D and Metformin against hematological, biochemical and histopathological alterations in induced diabetic rats. Ann Vet Anim Sci. 2020; 7 (1): 1-14. [CrossRef]