Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate

Abstract

In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. Therefore anti-inflammatory effect of MI-1 on rat acetic acid induced ulcerative colitis (UC) model was aimed to be discovered. The anti-inflammatory effects of MI-1 (2.7 mg/kg daily) compared to reference drug Prednisolone (0.7 mg/kg daily) after 14-day usage were evaluated on macro- and light microscopy levels and expressed in 21-grade scale. Redox status of bowel mucosa was also estimated. It was shown that in UC group the grade of total injury (GTI) was equal to 9.6 (GTIcontrol = 0). Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. MI-1 restored colon mucosa integrity and decreased mucosa inflammation down to GTI = 0.5 and leveled PCG and SOD. Thus, MI-1 possessed anti-inflammatory properties, which were more expressed that Prednisolone ones, as well as normalized mucosa redox balance, and so has a prospect for correction of inflammatory processes.

Water-Soluble Pristine C60 Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat

“…However, it affects the cell redox state because of a close relationship with numerous other signalings. For example, growth factor receptor inhibitors have been shown to release anti-inflammatory and anti-fibrotic activity also exhibit antioxidant one [ 69 , 70 ]. Although there are no proven anti-fibrotic therapeutics, numerous studies are underway to identify new ones and to establish anti-fibrotic activity for popular treatments of liver diseases accompanied by its fibrous degeneration [ 71 ].…”

Влияние 5-Амино-4-(1,3-Бензотиазол-2-Ин)-1-(3-Метоксифенил)-1,2-Дигидро-3h-Пиррол-3-Она На Состояние Органов Пищеварения При Экспериментальном Раке Толстого Кишечника Крыс

“…1) [2]. Ýòî ñîåäèíåíèå îáëàäàåò ïðîòèâîîïóõîëåâîé àêòèâ-íîñòüþ, ñðàâíèìîé ñ òàêîâîé êëàññè÷åñêîãî ïðåïàðàòà 5-ôòîð-óðàöèëà [12].…”

“…Âëèÿíèå Ä1 íà îðãàíû ïèùåâàðåíèÿ êðûñ èññëåäîâàëè ïðè ââå-äåíèè äàííîãî ñîåäèíåíèÿ â äîçå 2,3 ìã/êã (÷òî ïðè óñ-ëîâèè ïîëíîãî âñàñûâàíèÿ ïðåäïîëàãàåò êîíöåíòðàöèþ â êðîâè 10 -4 Ì), ðàñòâîðåííîãî â ðàñòèòåëüíîì ìàñëå, ñîäåðaeàùåãî 15 % ÄÌÑÎ (âñåãî 0,1 ìë), ïåðîðàëüíî åaeåäíåâíî â òå÷åíèå 7 è 27 íåäåëü. Îïóõîëè òîëñòîãî êèøå÷íèêà èíäóöèðîâàëè ñîãëàñíî [12,14]. 1,2-Äèìå-òèëãèäðàçèí (ÄÌÃ) (Acros Organics, USA) (20 ìã/êã â 0,1 ìë ôèçèîëîãè÷åñêîãî ðàñòâîðà) ââîäèëè ïîäêîaeíî åaeåíåäåëüíî â òå÷åíèå ïåðâûõ 20 íåäåëü ýêñïåðèìåíòà, ÷òî ÿâëÿåòñÿ äîñòàòî÷íûì äëÿ íåîáðàòèìîé èíäóêöèè ðàçâèòèÿ îïóõîëåé òîëñòîãî êèøå÷íèêà ïðàêòè÷åñêè â 100 % ñëó÷àåâ.…”

“…Ïðåäûäóùèå èññëåäîâàíèÿ [12] ïîêàçàëè, ÷òî Ä1 ïðîÿâëÿåò ïðîòèâîîïóõîëåâóþ àêòèâíîñòü, âåðîÿòíî, â òîì ÷èñëå è ÷åðåç áëîêàäó ðåöåïòîðîâ ê EGF è VEGF, ïîäîáíî äðóãèì âåùåñòâàì, èìåþùèì ïðîòèâîîïóõîëå-âóþ àêòèâíîñòü ïðè ÄÌÃ-èíäóöèðîâàííîì êàíöåðîãå-íåçå [13]. Ââåäåíèå Ä1 ÷àñòè÷íî íèâåëèðóåò ïîñëåäñò-âèÿ âîçäåéñòâèÿ êàíöåðîãåíà, óìåíüøàÿ ïðîÿâëåíèÿ âîñïàëèòåëüíûõ ðåàêöèé ñëèçèñòîé îáîëî÷êè aeåëóäêà è êèøå÷íèêà è ñïîñîáñòâóÿ ïðèáëèaeåíèþ ê íîðìå èõ èç-ìåíåííîãî ìîðôîôóíêöèîíàëüíîãî ñîñòîÿíèÿ, ïðè ýòîì ïðîòåêòîðíûé ýôôåêò äàííîãî ñîåäèíåíèÿ áîëåå âûðà-aeåí ïî îòíîøåíèþ ê aeåëóäêó, à òàêaeå ïðè äëèòåëüíîì (íà÷èíàÿ ñ 21 íåäåëè îïûòà) ïðèìåíåíèè äàííîãî ñî-åäèíåíèÿ.…”

“…1) [2]. Ýòî ñîåäèíåíèå îáëàäàåò ïðîòèâîîïóõîëåâîé àêòèâ-íîñòüþ, ñðàâíèìîé ñ òàêîâîé êëàññè÷åñêîãî ïðåïàðàòà 5-ôòîð-óðàöèëà [12].Èñõîäÿ èç ýòîãî, öåëüþ íàøåé ðàáîòû ÿâëÿåòñÿ èçó-÷åíèå âîçäåéñòâèÿ ïðîèçâîäíîãî ïèððîëà Ä1 íà ñëèçè-ñòóþ îáîëî÷êó aeåëóäêà, òîùåé êèøêè è ïå÷åíü. …”