Mechanism of taurine ameliorating cyclophosphamide-induced immunosuppression and protecting renal immune function in mice

doi:10.16098/j.issn.0529-1356.2026.06.014

PDF(20455 KB)

Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (5) : 622-630. DOI: 10.16098/j.issn.0529-1356.2026.06.014

Histology and embryology and Developmental Biology

Mechanism of taurine ameliorating cyclophosphamide-induced immunosuppression and protecting renal immune function in mice

GAO Hui-jie¹, XU Qing-qing¹, HU Yu-lian², WANG Qi¹, LIU Chao¹, REN Yan^1*

Author information +

History +

Abstract

Objective To explore the protective effect of taurine（TAU） on cyclophosphamide (CTX)-induced immunosuppression and renal immune microenvironment disorders in mice, and clarify its molecular mechanism regulating the PI3K/Akt signaling pathway. Methods Sixty ICR mice were randomly divided into control group, CTX group, low-dose taurine group (TAU-L, 100 mg/kg) and high-dose taurine group (TAU-H, 400 mg/kg), with 15 mice in each group. The control group was intraperitoneally injected with 0.2 ml normal saline daily for 12 consecutive days. The CTX group was injected with 0.2 ml normal saline for the first 7 days, and then intraperitoneally injected with 0.2 ml CTX (80 mg/kg) from day 8 to day 12 for 5 consecutive days to establish the model. The TAU-L and TAU-H groups were intraperitoneally injected with 0.2 ml taurine at the corresponding concentrations daily for 12 consecutive days, and synchronously injected with 0.2 ml CTX (80 mg/kg) from day 8 to day 12. The body weight growth rate, immune organ indices, and delayed-type hypersensitivity (DTH) intensity were measured. Routine blood test and biochemical detection were used to determine peripheral blood immune cell count, serum total protein (TP), IgM, interleukin (IL)-10 and tumor necrosis factor α (TNF-α) levels. HE staining was used to observe the pathological morphology of spleen and kidney. The activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in kidney were detected. Real-time PCR and immunohistochemistry were used to detect the mRNA and protein expressions of PI3K/Akt pathway-related molecules in spleen and kidney. Results Compared with the control group, the CTX group showed significantly decreased immune organ indices, DTH intensity, peripheral blood immune cell count, serum IgM and TP levels, increased IL-10 level and decreased TNF-α level (P<0.05 or P<0.0001); Abnormal pathological morphology of spleen and kidney, decreased renal SOD activity and increased MDA content (P<0.05); Down-regulated expressions of PI3K/Akt pathway-related molecules in spleen and kidney (P<0.05 or P<0.01). The above indicators were significantly improved in the high-dose taurine group (P<0.05), while some indicators in the low-dose taurine group were improved without statistical significance (P>0.05). Conclusion Taurine can activate the PI3K/Akt signaling pathway to improve CTX-induced immunosuppression and renal immune microenvironment disorder, enhance renal antioxidant capacity.

Key words

Taurine / Cyclophosphamide / Renal immune microenvironment / Phosphoinositide 3-kinase/protein kinase B pathway / Real-time PCR / Mouse

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

GAO Hui-jie, XU Qing-qing, HU Yu-lian, WANG Qi, LIU Chao, REN Yan. Mechanism of taurine ameliorating cyclophosphamide-induced immunosuppression and protecting renal immune function in mice[J]. Acta Anatomica Sinica. 2026, 57(5): 622-630 https://doi.org/10.16098/j.issn.0529-1356.2026.06.014

References

［1］Waz S, Heeba GH, Hassanin SO, et al. Nephroprotective effect of exogenous hydrogen sulfide donor against cyclophosphamide-induced toxicity is mediated by Nrf2/HO-1/NF-κB signaling pathway ［J］. Life Sci, 2021, 264: 118630.

［2］Ahlmann M, Hempel G. The effect of cyclophosphamide on the immune system: implications for clinical cancer therapy ［J］. Cancer Chemother Pharmacol, 2016, 78 (4): 661-671.

［3］Zhu L, Luo C, Ma C, et al. Inhibition of the NF-κB pathway and ERK-mediated mitochondrial apoptotic pathway takes part in the mitigative effect of betulinic acid on inflammation and oxidative stress in cyclophosphamide-triggered renal damage of mice ［J］. Ecotoxicol Environ Saf, 2022, 246: 114150.

［4］Cao L, Du J, Nie Z, et al. Alteration of endoplasmic reticulum stress, inflammation and anti-oxidative status in cyclophosphamide-damaged liver of Nile tilapia (Oreochromis niloticus) ［J］. Comp Biochem Physiol C Toxicol Pharmacol, 2022, 254: 109271.

［5］Wang Y, Ni W, Jin X, et al. Vitexin-2-O-rhamnoside improves immunosuppression, oxidative stress, and phosphorylation of PI3K/Akt signal pathway in cyclophosphamide treated mice ［J］. Eur J Pharmacol, 2022, 925: 174999.

［6］Zhang X, Ming Y, Fu X, et al. PI3K/Akt/p53 pathway inhibits infectious spleen and kidney necrosis virus infection by regulating autophagy and immune responses ［J］. Fish Shellfish Immunol, 2022, 120: 648-657.

［7］Rafiee Z, García-Serrano AM, Duarte JMN. Taurine supplementation as a neuroprotective strategy upon brain dysfunction in metabolic syndrome and diabetes ［J］. Nutrients, 2022, 14 (6): 1292.

［8］Misirliolu M, Bingl , Gen C, et al. Investigation of taurine and aqueous garlic extract diet supplementation effect on the healing of rat osteoporotic fractures ［J］. Turk J Med Sci, 2023, 53 (1): 29-39.

［9］Xie YT, Wang XD, Ye HF, et al. Research progress on anti-aging and biosynthesis of taurine ［J］. Chinese Bulletin of Life Sciences, 2025, 37(8): 983-991. (in Chinese)

谢泳桃,王旭东,叶海峰,等.牛磺酸抗衰老及其生物合成研究进展［J］.生命科学, 2025, 37(8): 983-991.

［10］Fang H, Meng F, Piao F, et al. Effect of taurine on intestinal microbiota and immune cells in Peyer’s patches of immunosuppressive mice ［J］. Adv Exp Med Biol. 2019，1155:13-24.

［11］Ma Y, Zhang Y, Li R, et al. Mechanism of taurine reducing inflammation and organ injury in sepsis mice ［J］. Cell Immunol, 2022, 375: 104503.

［12］Zhao YZ, Wang YL, Yu Y. Immunoenhancement effect of cinobufagin on macrophages and the cyclophosphamide-induced immunosuppression mouse model ［J］. Int Immunopharmacol, 2024, 131: 111885.

［13］Lu Z, Liao H, Zhang M, et al. Tanshinone I inhibits the functions of T lymphocytes and exerts therapeutic effects on delayed-type hypersensitivity reaction via blocking STATs signaling pathways ［J］. Eur J Pharmacol, 2024, 985: 177128.

［14］Fernandez ME, Bernier M, Price NL, et al. Is taurine an aging biomarker ［J］ ? Science, 2025, 388 (6751): eadl2116.

［15］VanHook AM. Suppressing appetite with taurine ［J］. Sci Signal, 2024, 17 (854): eadt0770.

［16］Uyanga VA, Oke EO, Amevor FK, et al. Functional roles of taurine, L-theanine, L-citrulline, and betaine during heat stress in poultry ［J］. J Anim Sci Biotechnol, 2022, 13 (1): 23.

［17］Liu JX, Guo HY, Zhu KC, et al. Effects of exogenous taurine supplementation on the growth, antioxidant capacity, intestine immunity, and resistance against Streptococcus agalactiae in juvenile golden pompano (Trachinotus ovatus) fed with a low-fishmeal diet ［J］. Front Immunol, 2022, 13: 1036821.

［18］Zhang L, Zhang L, Liang H, et al. Effects of taurine and vitamin C on the improvement of antioxidant capacity, immunity and hypoxia tolerance in Gibel Carp (Carrassius auratus gibelio) ［J］. Antioxidants (Basel), 2024, 13 (10): 1169.

［19］Li Q, Gao J, Hu R, et al. Expression of phosphatidylinositol-3 kinase/protein kinase B/FoxO1 signal pathway and interleukin-17 in experimental autoimmune encephalomyelitis in mice ［J］. Acta Anatomica Sinica, 2021, 52 (3): 358-364. (in Chinese)

李倩,高杰,胡蓉,等.磷脂酰肌醇-3激酶/蛋白激酶B/FoxO1信号通路和白细胞介素17在小鼠实验性自身免疫性脑脊髓炎中的表达变化［J］.解剖学报,2021,52(3):358-364.

［20］Kim KC, Lee IK, Kang KA, et al. 7,8-Dihydroxyflavone suppresses oxidative stress-induced base modification in DNA via induction of the repair enzyme 8-oxoguanine DNA glycosylase-1 ［J］. Biomed Res Int, 2013, 2013: 863720.

［21］Jong CJ, Sandal P, Schaffer SW. The role of taurine in mitochondria health: more than just an antioxidant ［J］. Molecules, 2021, 26 (16): 4913.

［22］Sirdah MM. Protective and therapeutic effectiveness of taurine in diabetes mellitus: a rationale for antioxidant supplementation ［J］. Diabetes Metab Syndr, 2015, 9 (1): 55-64.

［23］Baliou S, Adamaki M, Ioannou P, et al. Protective role of taurine against oxidative stress (Review) ［J］. Mol Med Rep, 2021, 24 (2): 605.

［24］Chen C, Xia S, He J, et al. Roles of taurine in cognitive function of physiology, pathologies and toxication ［J］. Life Sci, 2019, 231: 116584.

［25］Liu D, Lin J, He W, et al. Selenium and taurine combination is better than alone in protecting lipopolysaccharide-induced mammary inflammatory lesions via activating PI3K/Akt/mTOR signaling pathway by scavenging intracellular ROS ［J］. Oxid Med Cell Longev, 2021, 2021: 5048375.