The Relationship between Caspase-3, -6 Expression and Morphological Changes in Kidneys of Cows

Introduction. Cow kidneys are exposed to the impact of industrial factors, which is manifested in development of the various nephropathies with systemic effects on organism. The kidneys are the main organs responsible for homeostasis by regulating osmolarity, mineral balance, and acid-base balance in organism through the excretion of water and inorganic electrolytes. Renal pathology often has latent character and is diagnosed postmortem. Significant destructive changes, including cell death, are often detected in lactating cows due to high metabolic load they undergo. Caspase pathway is one of the pathways in the complex apoptotic signaling cascade. Unfortunately, the expression of caspases in bovine kidneys has not been yet described in the literature. The aim of the study is to describe the relationship between the expression of caspase-3 and caspase-6 and the pathological changes in the kidneys of high-yielding cows.
Materials and Methods. A morphological study of renal samples from high-yielding cows (4–6 lactations, 7–8 years old, n=4) was conducted at the Ural Federal Agrarian Scientific Research Center, Ural Branch of the Russian Academy of Sciences in the period from 2023 to 2025. Standard histological techniques including hematoxylin and eosin staining and Mallory’s trichrome staining were used. Immunohistochemical analysis of the samples using antibodies to caspase-3, and -6 was performed.
Results. It was found that in the kidneys of 7–8-year-old cows there develop the destructive processes including renal failure, inflammatory reactions, and sclerotic and microcirculatory disorders. The observed conditions are associated with high expression of caspase-6 at the level of the renal tubules, which confirms damage to the renal parenchyma. Caspase-3 is expressed primarily in the renal tubules and in renal stroma elements, which indicates intensification of apoptotic processes across the entire organ.
Discussion and Conclusion. The destructive processes revealed in the kidneys of high-yielding cows are likely to be associated not only with the age but also with the high metabolic load imposed on the organism during lactation. The research findings substantiate the need for further study of pro-apoptotic factors due to their influence on the development of various pathologies in cattle.

1. Evglevsky AA, Evglevskaya EP, Mikhaylova II, Vanina NV, Erigenskaya NF, Suleimanova TA. Disturbance of Acid-Base Balance in the Cow: Causes, Consequences and Treatment. Veterinary Pathology. 2017;(1(59)):53–58. (In Russ.).

2. İssi M, Gül Y, Başbuğ O. Evaluation of Renal and Hepatic Functions in Cattle with Subclinical and Clinical Ketosis. Turkish Journal of Veterinary and Animal Sciences. 2016;40:47–52. https://doi.org/10.3906/vet-1505-16

3. Pak LB, Dubikov AI, Kabanceva TA, Vasilyuk AA, Grigoryan OM. Apoptosis and Nephropathies. Nephrology. 2013;17(4):36–43. (In Russ.).

4. Yang B, Lan S, Dieudé M, Sabo-Vatasescu JP, Karakeussian-Rimbaud A, Turgeon J, et al. Caspase-3 is a Pivotal Regulator of Microvascular Rarefaction and Renal Fibrosis after Ischemia-Reperfusion Injury. Journal of the American Society of Nephrology. 2018;29(7):1900–1916. http://doi.org/10.1681/ASN.2017050581

5. Hörbelt M., Lee S.Y., Mang H.E., Knipe N.L., Sado Y., Kribben A., Sutton T.A. Acute and chronic microvascular alterations in a mouse model of ischemic acute kidney injury. American Journal of Physiology. 2007;293(3):688–695. https://doi.org/10.1152/ajprenal.00452.2006

6. Forbes JM, Hewitson TD, Becker GJ, Jones CL. Ischemic Acute Renal Failure: Long-Term Histology of Cell and Matrix Changes in the Rat. Kidney International. 2000;57(6):2375–2385. https://doi.org/10.1046/j.1523-1755.2000.00097.x

7. Ul Aabdin Z, Cheng X, Dai H, Wang Y, Sahito B, Roy AC, et al. High-Concentrate Feeding to Dairy Cows Induces Apoptosis via the NOD1/Caspase-8 Pathway in Mammary Epithelial Cells. Genes. 2020;11(1):107. https://doi.org/10.3390/genes11010107

8. Homsi E, Janino P, de Faria JBL. Role of Caspases on Cell Death, Inflammation, and Cell Cycle in Glycerol-Induced Acute Renal Failure. Kidney International. 2006;69(8):1385–1392. https://doi.org/10.1038/sj.ki.5000315

9. Tao Y, Zafar I, Kim J, Schrier RW, Edelstein CL. Caspase-3 Gene Deletion Prolongs Survival in Polycystic Kidney Disease. Journal of the American Society of Nephrology. 2008;19(4):749–755. https://doi.org/10.1681/ASN.2006121378