Diphenhydramine modulates cytokines and induces apoptosis in experimental acute pancreatitis.
In this study, we investigated the therapeutic potential of diphenhydramine (DPH), a H(1) receptor antagonist, on taurocholate-induced acute pancreatitis and the underlying mechanisms involved. Rats were randomly divided into sham-operated, model, DPH-treated, octreotide-treated and the DPH plus octreotide combination therapy groups (n = 30 per group). Animals were sacrificed 3, 6 and 24 h after modeling and drug administration (n = 10 per time point) and sera, pancreas and lungs were harvested for further studies. DPH and octreotide monotherapy relieved histopathological injuries in multiple organs when compared to the model group. Combination therapy (DPH + octreotide) demonstrated better therapeutic potential than monotherapy. Data indicated that combination therapy had a better ability to reduce average mortality rates in rats, decrease the number of inflammatory cells, attenuate necrosis, upregulate the levels of amylase, TNF-alpha and IL-8 and downregulate the levels of IL-10 in the serum. Moreover, enhanced expression of Bax in the pancreas and lung were recorded suggesting a pro-apoptotic mechanism involved in the therapeutic potential of DPH. Our study demonstrated the therapeutic potential of DPH in acute pancreatitis and suggested a novel strategy for clinical management of this disease.
You
N
N
Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P.R. China.
Tao
K
K
Zhao
W
W
Bao
P
P
Li
R
R
You
H
H
Zhang
M
M
Gao
Z
Z
Gao
Z
Z
Dou
K
K
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000097:blood*; D004155:Diphenhydramine / Q000494:pharmacology / Q000627:therapeutic use*; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D015282:Octreotide / Q000627:therapeutic use; D010195:Pancreatitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011654:Pulmonary Edema / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000032:analysis
C494828:Bax protein, rat; D016207:Cytokines; D006634:Histamine H1 Antagonists; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D016753:Interleukin-10; D004155:Diphenhydramine; D000681:Amylases; D015282:Octreotide