Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death.
Yu Ji Jiang, Sheng Cui, Kang Luo, Jun Ding, Qi Yan Nan, Shang Guo Piao, Mei Ying Xuan, Hai Lan Zheng, Yong Jie Jin, Ji Zhe Jin, Jung Pyo Lee, Byung Ha Chung, Bum Soon Choi, Chul Woo Yang, Can Li
Author Information
Yu Ji Jiang: Department of Nephrology, Yanbian University Hospital, Yanji, China.
Sheng Cui: Department of Nephrology, Yanbian University Hospital, Yanji, China.
Kang Luo: Department of Nephrology, Yanbian University Hospital, Yanji, China.
Jun Ding: Department of Nephrology, Yanbian University Hospital, Yanji, China.
Qi Yan Nan: Department of Nephrology, Yanbian University Hospital, Yanji, China.
Shang Guo Piao: Department of Nephrology, Yanbian University Hospital, Yanji, China.
Mei Ying Xuan: Department of Nephrology, Yanbian University Hospital, Yanji, China.
Hai Lan Zheng: Department of Nephrology, Yanbian University Hospital, Yanji, China.
Yong Jie Jin: Department of Nephrology, Yanbian University Hospital, Yanji, China.
Ji Zhe Jin: Department of Nephrology, Yanbian University Hospital, Yanji, China.
Jung Pyo Lee: Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
Byung Ha Chung: Transplantation Research Center, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Bum Soon Choi: Transplantation Research Center, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Chul Woo Yang: Transplantation Research Center, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Can Li: Department of Nephrology, Yanbian University Hospital, Yanji, China.
BACKGROUND/AIMS: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. METHODS: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). RESULTS: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. CONCLUSION: Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.
