Cerulein-induced chronic pancreatitis in Swiss albino mice: An improved short-term model for pharmacological screening

Bansod, Sapana; Khurana, Amit; Godugu, Chandraiah

doi:10.1016/j.vascn.2019.01.002

Cited by 15 publications

(18 citation statements)

References 49 publications

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“…Malondialdehyde (MDA), nitrite, and GSH contents were measured in pancreatic tissue by following the previously described method 27,28 . Pancreatic tissue samples were homogenized in phosphate buffer and homogenates were used for the estimation of MDA levels and remaining tissue homogenate were centrifuged at 9168 g for 10 minutes at 4°C and the supernatant was used for the estimation of nitrite and GSH content in the pancreas.…”

Section: Methodsmentioning

confidence: 99%

Borneol protects against cerulein‐induced oxidative stress and inflammation in acute pancreatitis mice model

Bansod

Chilvery

Saifi

et al. 2020

Environmental Toxicology

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Borneol is a commonly used flavouring substance in traditional Chinese medicine, which possesses several pharmacological activities including analgesic, antiinflammatory, and antioxidant properties. The aim of this study was to investigate the effects of borneol on cerulein‐induced acute pancreatitis (AP) model. Swiss albino mice were pretreated with borneol (100 and 300 mg/kg) daily for 7 days, before six consecutive injections of cerulein (50 μg/kg/hr, intraperitoneally). The protective effect of borneol was studied by biochemical, enzyme linked immunosorbent assay, histological, immunoblotting, and immunohistochemical analysis. Oral administration of borneol significantly attenuated pancreatic damage by reducing amylase, lipase levels and histological changes. Borneol attenuated cerulein‐induced oxidative‐nitrosative stress by decreasing malondialdehyde, nitrite levels, and elevating reduced glutathione levels. Pancreatic inflammation was ameliorated by inhibiting myeloperoxidase activity and pro‐inflammatory cytokine (Interleukins and TNF‐α) levels. Furthermore, borneol administration significantly increased nuclear factor E2‐related factor 2 (Nrf2), superoxide dismutase (SOD1) expression and reduced phospho‐NF‐κB p65 expression. Treatment with borneol significantly inhibited TNF‐α, IL‐1β, IL‐6, and inducible nitric oxide synthase expression in cerulein‐induced AP mouse model. Together, these results indicate that borneol which is currently used as US‐FDA approved food adjuvant has the potential to attenuate cerulein‐induced AP possibly by reducing the oxidative damage and pancreatic inflammation by modulating Nrf2/NF‐κB pathway.

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Section: Methodsmentioning

confidence: 99%

Borneol protects against cerulein‐induced oxidative stress and inflammation in acute pancreatitis mice model

Bansod

Chilvery

Saifi

et al. 2020

Environmental Toxicology

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“…The expression of proteins was evaluated by western blot analysis. The samples for western blot were prepared as described earlier . A total of 20 μg of protein was loaded onto polyacrylamide gel, and the proteins were separated by SDS‐PAGE (sodium dodecyl sulfate‐polyacrylamide gel electrophoresis) and transferred onto the nitrocellulose membranes at 17 V for 55 min.…”

Section: Methodsmentioning

confidence: 99%

“…The samples for western blot were prepared as described earlier. 24,25 A total of 20 μg of protein was loaded onto polyacrylamide gel, and the proteins were separated by SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and transferred onto the nitrocellulose membranes at 17 V for 55 min. The membranes were blocked with 3% BSA and washed with TBS-T for 10 min thrice and subsequently incubated overnight with the respective primary antibodies (1:1000 dilution) at 4 C. Next day, the membranes were washed with TBS-T and incubated with secondary antibody (1:20,000 dilution) at room temperature for 1 hr.…”

Section: Western Blot Analysismentioning

confidence: 99%

Withaferin A ameliorates renal injury due to its potent effect on inflammatory signaling

et al. 2019

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Chronic kidney disease (CKD) is one of the major global health concerns and is responsible for end‐stage renal disease (ESRD) complications. Inflammation plays a pivotal role in the progression of CKD. In the present study, we evaluated the renoprotective effects of a potent immunomodulator steroidal lactone, Withaferin A (WfA), in an animal model of renal injury (unilateral ureteral obstruction, UUO) and further investigated if the inhibition of inflammatory signaling can be a useful approach to reduce renal injury. Animals were randomly divided into five groups: Sham control, UUO control, WfA control, WfA low dose (1 mg/kg), and WfA high dose (3 mg/kg). Oxidative stress was measured by the estimation of reduced glutathione and lipid peroxidation levels. H&E and Picrosirius Red staining were performed to assess the extent of histological damage and collagen deposition. Furthermore, the molecular mechanism of the WfA effects was explored by immunohistochemistry, enzyme‐linked immunosorbent assay, multiplex analysis of transforming growth factor β (TGF‐β) pathway, and an array of inflammatory cytokines/chemokines. Interestingly, our pharmacological intervention significantly attenuated tissue collagen, inflammatory signaling, and macrophage signaling. WfA intervention abrogated the inflammatory signaling as evident from the modulated levels of chemokines and cytokines. The levels of TGF‐β along with downstream signaling molecules were also attenuated by WfA treatment as revealed by inhibition in the expression of TGF‐β1, TGF‐β2, p‐Smad2, p‐Smad3, total Smad4, p‐Akt, and p‐ERK. We, to the best of our knowledge, prove for the first time that WfA has potential renoprotective activity against UUO‐induced nephropathy due to its outstanding anti‐inflammatory properties.

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“…Doses of IMT were selected on the basis of previous literature [20]. However, cerulein needed minimum 12 hr to produce maximum in ammatory response, IMT was given every other day after cerulein exposures for the period of 3 weeks [19].…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Inhibition of DDR1 and DDR2 receptors: The Potential Therapeutic Option to Treat Pancreatic Fibrosis Demonstrated in Experimental Chronic Pancreatitis Model

Bansod¹,

Saifi²,

Godugu³

2020

Preprint

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Discoidin domain receptors (DDR1 and DDR2) are the collagen receptors of the family tyrosine kinases, which play significant role in the diseases like inflammation, fibrosis and cancer. Chronic pancreatitis (CP) is a fibro-inflammatory disease in which recurrent pancreatic inflammation leads to pancreatic fibrosis.Methods: In the present study for the first time, we have investigated the role of DDR1 and DDR2 in cerulein-induced CP. Pancreatic DDR1 and DDR2 expression was examined by immunoblotting and immunostaining analysis. Subsequently, the protective effects of selective DDR1 and DDR2 inhibitor, imatinib (IMT) was investigated in CP mice as a therapeutic intervention.Results: Activated pancreatic stellate cells (PSCs) and CP mice showed significant upregulation of DDR1 and DDR2 expression. Pharmacological intervention with IMT effectively downregulated DDR1 and DDR2 expression. Further, we found that pancreatic injury, inflammation, extracellular matrix (ECM) deposition and PSCs activation were significantly inhibited by IMT. Further, we found a significant inhibition of TGF-β1/Smad signaling pathway by IMT and showed its protective effects against CP and associated fibrosis.Conclusions: Taken together, these results suggest that inhibition of DDR1 and DDR2 controls pancreatic inflammation and fibrosis, which could represent an attractive and promising therapeutic strategy for the treatment of CP.

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Cerulein-induced chronic pancreatitis in Swiss albino mice: An improved short-term model for pharmacological screening

Cited by 15 publications

References 49 publications

Borneol protects against cerulein‐induced oxidative stress and inflammation in acute pancreatitis mice model

Borneol protects against cerulein‐induced oxidative stress and inflammation in acute pancreatitis mice model

Withaferin A ameliorates renal injury due to its potent effect on inflammatory signaling

Inhibition of DDR1 and DDR2 receptors: The Potential Therapeutic Option to Treat Pancreatic Fibrosis Demonstrated in Experimental Chronic Pancreatitis Model

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