Effects of Lycium barbarum glycopeptide on renal and testicular injury induced by di(2-ethylhexyl) phthalate

Abstract

Di(2-ethylhexyl) phthalate (DEHP) is a common environmental pollutant with renal and reproductive toxicity. Lycium barbarum glycopeptide (LbGp) is the main active component of Lycium barbarum, which can protect the kidney and promote reproduction. Autophagy and apoptosis are the regulatory mechanisms of cell adaptation to external stress. This study investigated whether DEHP and LbGp affect kidney and testis by regulating autophagy and apoptosis. DEHP induced apoptosis in human embryonic kidney-293 (HEK-293) cells and human kidney-2 (HK-2) cells, as well as glomerular enlargement, enhanced renal autophagy and inflammation, decreased testicular germ cells, and enhanced testicular autophagy. LbGp reduced apoptosis in HEK-293 cells and HK-2 cells, reduced glomerular enlargement and renal inflammation, enhanced renal autophagy, increased testicular germ cells, and alleviated testicular autophagy. These results suggested that DEHP induced inflammation to cause kidney injury, mildly enhanced renal autophagy, and also induced excessive autophagy, leading to testicular injury. LbGp reduced inflammation and appropriately enhanced autophagy to alleviate renal injury and also reduced excessive autophagy to alleviate testicular injury. Silent information regulator 1 (SIRT1)/forkhead box O3a (FoxO3a)-mediated autophagy and p38 mitogen-activated protein kinase (p38 MAPK)-mediated inflammation played important roles.

Green Tea Polyphenols Alleviate Kidney Injury Induced by Di(2-Ethylhexyl) Phthalate in Mice

“…Here, we revealed that the creatinine levels of DEHP-exposed mice were significantly higher than those of the control group. However, our previous study [21] did not discuss the deterioration of renal function in the model group due to the short time (2 weeks) required for establishing the DEHP model. Li et al [36] reported that mice treated with 1,000 mg/kg/bw DEHP or 500 mg/kg/ bw DEHP showed significantly higher serum creatinine, urea nitrogen, and uric acid levels than untreated mice.…”

“…First, we found that the kidney indices of the model group were significantly lower than those of the control group, whereas the kidney indices of the treatment group receiving GTPs reversed DEHP-induced kidney damage. We have previously reported [21] that DEHP can reduce the kidney indices of the mice in the DEHP model group. Here, we revealed that the creatinine levels of DEHP-exposed mice were significantly higher than those of the control group.…”

“…Considering the insolubility of DEHP in water but its solubility in oil, we dissolved DEHP in corn oil to administer it via gavage to mice. The administration dosage was determined by referring to our previous investigation [21] and empirical evidence of LD50 of 30 g/kg for oral DEHP in mice [22]. A thorough review of relevant literature was used to determine the GTP dosage via gavage [23], resulting in a low and more pragmatic dose.…”

“…In total, 10 glomeruli were measured per sample, and the average thickness for each group was calculated. The integrated optical density (IOD) of pathological images was measured and analyzed using Image-Pro Plus 6.0 (Media Cybernetics, Rockville, MD, USA) as reported previously [21].…”

Green tea polyphenols alleviate di-(2-ethylhexyl) phthalate-induced liver injury in mice

“…After 1 wk of acclimatization, 50 mice were randomly assigned into the following five groups (10 mice/group): Control group, administered with 0.2 mL distilled water; model group, administered with 0.2 mL corn oil and DEHP (1500 mg/kg bodyweight); treatment group, administered with 0.2 mL corn oil and DEHP (1500 mg/kg bodyweight), followed by administration of 0.2 mL GTPs (70 mg/kg bodyweight) after 1 h; oil group, administered with 0.2 mL corn oil; GTP group, administered with 0.2 mL GTP (70 mg/kg bodyweight). Based on our previous study, DEHP[ 25 ] and GTPs[ 26 ] were gavaged. The doses were adjusted weekly based on the bodyweight of the mice.…”