Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in bladder ischemia–reperfusion injury in rats

Abstract

The aim of the present study was to evaluate the protective effects of the NF-кB inhibition with pyrrolidine-dithiocarbamate (PDTC) in ischemia-reperfusion (I/R) injury in the rat bladder. Twenty-four Sprague-Dawley male rats were divided into three groups. Group I; (n = 8) control, group II; (n = 8) I/R group; group III (n = 8) I/R and PDTC treatment. Superoxide dismutase (SOD), catalase (CAT), and gluatathione-S-transferase (GST) enzymes was studied in bladder tissue. Lipid peroxidation (as TBARS) levels in tissue homogenate were measured with thiobarbituric acid reaction. All the slides were stained with NF-кB, p53 and HSP60 immunohistochemistry for detection genome destruction and tissue stress, respectively. Our results show that the mean TBARS levels were significantly higher in group II (p < 0.05). The TBARS levels were significantly decreased in group III compared with the group II (p < 0.05). CAT, SOD and GST activities were decreased in group II, but these enzymes levels were significantly increased in group III according to the group II (p < 0.05). Under microscopic evaluation NF-кB expression increased significantly in group II compared to the group I (p < 0.05) and then decreased in group III (p < 0.05). HSP60 and p53 expression in group II was increased significantly compared with group I. Under microscopic evaluation we detected that HSP60 and p53 expression was increased significantly in group II compared with group I. In group III PDTC administration was decreased the HSP60 and p53 expression, this difference was statistically significant (p < 0.05). The results of the present study have demonstrated that NF-кB inhibition with PDTC protects and provides beneficial effects on ischemia/reperfusion stress related bladder tissue destruction.

Topical emulsion containing pyrrolidine dithiocarbamate: effectiveness against ultraviolet B irradiation-induced injury of hairless mouse skin

“…Indeed, this protective effect of PDTC on GSH levels has also been reported in others models in rats, such as lipopolysaccharide‐induced hepatic injury, cisplatin‐induced testicular damage, ischaemia/reperfusion injury, and caecal ligation and puncture‐induced sepsis in rats . Moreover, supporting our results, PDTC restored the catalase activity in lipopolysaccharide‐induced oxidative stress, and in bladder ischaemia–reperfusion injury in rats …”

“…PDTC is a low‐molecular‐weight thiol compound with great therapeutic potential as an anti‐inflammatory and antioxidant . PDTC was initially regarded as a potent inhibitor of NF‐κB, and it has been studied as a strong antioxidant compound to counteract the toxic effects of ROS .…”

“…Topical delivery of antioxidant and anti‐inflammatory molecules is considered a promising strategy to reduce UVB irradiation‐induced skin damages . Pyrrolidine dithiocarbamate (PDTC) is a small molecule with relatively low cost though with important pharmacological activity such as antioxidant and anti‐inflammatory . Preclinical toxicity study has shown that PDTC is a safe drug .…”

Pyrrolidine dithiocarbamate inhibits enterovirus 71 replication by down-regulating ubiquitin–proteasome system

“…Pyrrolidine dithiocarbamate (PDTC) is a synthetic compound, which is largely used as antioxidant or nuclear factor kappa B (NF-B) inhibitor (Morais et al, 2010;Wiesener et al, 2011;Yucel et al, 2013). Previous studies have shown that PDTC could inhibit the replication of coxsackievirus B3 (CVB3), rhinovirus, influenza virus, and herpes simplex virus (Krenn et al, 2005;Qiu et al, 2013;Si et al, 2005;Uchide and Ohyama, 2003;Uchide et al, 2002;Wiesener et al, 2011), while the precise mechanism involved in the antiviral activity of PDTC has not been elucidated.…”

Novel intracellular N‐terminal truncated matrix metalloproteinase‐2 isoform in skeletal muscle ischemia‐reperfusion injury

“…To study the effect of PDTC on NTT‐MMP‐2 expression in our IRI model, we randomly divided mice into four groups ( N = 6/group), PDTC‐treated control, PDTC‐treated IRI, vehicle‐treated control, and vehicle‐treated IRI. Mice in the treatment group received a 100 μl intra‐peritoneal (IP) injection of PDTC (Sigma–Aldrich, Inc., St. Louis, MO) at 30 mg/ml 1 h prior to ischemic injury as previously described . Mice in the vehicle groups received an equivalent dose of saline before injury.…”