Sulfasalazine induces mitochondrial dysfunction and renal injury

Figures & data

Figure 1. Serum biochemistry of kidney injury biomarkers in sulfasalazine-treated animals. SSZ: sulfasalazine. Data are expressed as mean ± SD (n = 8). Asterisks indicate significantly different as compared with control group (**p < .01 and ***p < .001).

Figure 2. Animals weight gain (A) and kidney weight (B) were assessed after 14 d of sulfasalazine administration. SSZ: sulfasalazine. Data are given as mean ± SD (n = 8). Asterisks indicate significantly different as compared with control animals (*p < .05 and ***p < .001). Superscript “ns” indicates not significant as compared to control group (p > .05).

Figure 3. Kidney mitochondrial succinate dehydrogenase activity (SDA) (MTT assay) and photomicrographs of kidney histopathological changes in sulfasalazine-treated animals. MTT test revealed a significant decrease in mitochondrial SDA in the kidney of sulfasalazine-treated animals (mean ± SD, n = 8, and ***p < .001). Kidney photomicrographs showed tubular atrophy, necrosis, and interstitial inflammation in sulfasalazine-treated animals (B, C, and D) in comparison with control group (A). A: control (vehicle-treated), B: sulfasalazine 400 mg/kg/day); C and D: sulfasalazine 600 mg/kg/day).

Table 1. Kidney tissue ROS formation, lipid peroxidation, total antioxidant capacity, and glutathione content.

Treatment	ROS formation (fluorescent intensity, FI)	Lipid peroxidation (nmol of TBARS/mg kidney tissue)	GSH (µmol/mg kidney tissue)	Total antioxidant capacity (µmol of vitamin C equivalent)
Control	75432 ± 5276	1.71 ± 0.82	71.55 ± 6.22	89.22 ± 11.23
SSZ 400 (mg/kg)	154209 ± 11231*	3.44 ± 0.56*	56.33 ± 3.22*	36.49 ± 6.22*
SSZ 600 (mg/kg)	186532 ± 8638*	2.66 ± 0.61*	42.35 ± 6.27*	41.22 ± 3.44*

Note: Data are shown as mean ± SD (n = 8). SSZ: sulfasalazine.

Asterisk(*) indicates significantly different as compared to control group (p < .001).

Table 2. Renal injury score in sulfasalazine-treated rats.

Treatment	Focal necrosis	Tubular atrophy	Interstitial inflammation	Vascular congestion
Control	–	–	–	–
SSZ 400 (mg/kg)	+	+	+	+
SSZ 600 (mg/kg)	+	+	++	++

SSZ: sulfasalazine.

Figure 4. Mitochondrial depolarization (A), swelling (B), and ROS formation (C) in the kidney of sulfasalazine-treated animals. SSZ: sulfasalazine. Data are given as mean ± SD (n = 8). Asterisks indicate significantly different as compared with control group (*p < .05, **p < .01, and ***p < .001). Superscript “ns” indicates not significant as compared to control group (p > .05).

Figure 5. Mitochondrial glutathione content (A) and lipid peroxidation (B) in the kidney of sulfasalazine-treated animals. SSZ: sulfasalazine. Data are given as mean ± SD (n = 8). Superscript “ns” indicates not significant as compared to control. Asterisks indicate significantly different as compared to control (**p < .01 and ***p < .001).