Pathophysiology of Experimental Pancreatitis

Acute pancreatitis is a significant cause of morbidity, mortality, and hospitalization worldwide. The incidence of acute pancreatitis is on the rise. Owing to an incomplete understanding of the pathophysiology of acute pancreatitis, no targeted therapy is available for this disease. Hence, currently, the treatment revolves largely around supportive measures. Our limited understanding of the pathophysiology of acute pancreatitis is based on studies using experimental animal models and pancreatic cell‐based in vitro experiments. Several experimental models of acute pancreatitis have been developed in different species. However, lately most of the studies have been performed in murine models, for multiple reasons, the most important of which is the availability of strains of mice with different gene deletions. Although studies on these murine models have provided useful information on the initiating events of acute pancreatitis, these models do not mimic the progression of human pancreatitis. Studies suggest that acute pancreatitis begins in the pancreatic acinar cells. Premature activation of zymogens, inhibition of secretion, and activation of inflammatory pathways are observed in the pancreatic acinar cells within minutes of pathologic provocation. Other events such as increased endoplasmic reticulum stress, loss of mitochondrial potential, and autophagy dysfunction are also observed in pancreatic acinar cells, early on during acute pancreatitis. Eventually, these events lead to pancreatic acinar cell death and spread of inflammation to other organs. Uncontrolled systemic inflammation can lead to multiorgan failure. Studies in experimental models suggest that intra‐acinar trypsin activation, which has been considered central to the pathogenesis of acute pancreatitis for decades, results from colocalization of zymogens and lysosomes. Perturbed calcium signaling is believed to be involved in initiating pathologic changes. Although inhibition of trypsin provides significant protection from acinar cell death, recent studies suggest that events other than trypsin activation play a central role in pathogenesis of acute pancreatitis. Emerging evidence suggests that cathepsin B, in addition to playing an important role in trypsin activation, can play a role in activation of cell death pathways. Furthermore, data suggest that trypsin‐independent inflammation plays an important role in local and systemic injury. The ability to modulate the pathophysiology and progression of inflammation might improve the outcomes for patients

A triterpenoid acid, lantadene D from Lantana camara var. Aculeata

A novel triterpenoid, lantadene D, has been isolated from the leaves of the hepatotoxic plant Lantana camara var. aculeata. Its structure has been established as 22-β-isobutyroyloxy-3-oxoolean-12-en-28-oic acid

Protein-binding capacity of microquantities of tannins

The physiological effect of tannins is studied in terms of their protein-binding or precipitation capacity. A number of assays based on binding of hemoglobin or bovine serum albumin (BSA) and subsequent determination of unbound protein in supernatant or tannin in a protein-tannin complex are available but with various limitations. These methods are unable to estimate protein-binding capacity, if the quantity of tannin available is low. In the method reported here, tannins or other phenolics were applied on chromatography paper and reacted with BSA and unbound BSA was washed off. The protein in the tannin-protein complex was measured spectrophotometrically after staining with Ponceau S. It required microquantities of sample. Using this method the protein-binding capacity of total leaf extract and hydrolyzable and condensed tannins of Quercus incana, Q. semecarpofolia, and Q. dilatata was determined. The protein binding capacities of ellagic acid and quercetin (μg BSA/mg) were 297.3 and 78.0, respectively

Effect of polymorphic crystal forms of lantana toxins on icterogenic action in guinea pigs

A partially purified preparation of toxin isolated from lantana ( Lantana camara L., red variety) leaves, called fraction C, was obtained in two crystalline forms: form I, white, fluffy, rod-shaped and form II, irregular, polyhedral, shining crystals. The two forms differed in melting point behaviour and icterogenic action when administered orally to guinea pigs. Only form II was icterogenic to guinea pigs and was associated with decreased feed intake and faecal output, hepatomegaly, increase in plasma bilirubin level and acid phosphatase activity

Protein precipitation assay for quantitation of tannins: Determination of protein in tannin-protein complex

A protein precipitation method for the determination of tannins has been developed. The protein in the tannin-protein complexes was measured using the ninhydrin assay of amino acids released by alkaline hydrolysis of the complex. Standard protein and the complex were hydrolyzed with 13.5 n NaOH at 120°C for 20 min and the amino acids released were measured with ninhydrin. Tannins did not interfere in the determination of protein by ninhydrin assay. The bovine serum albumin (BSA) precipitated ( y;mg) increased linearly with increase in tannic acid ( x) from 0.2 to 0.9 mg ( y = 2.598 x − 0.258). The protein precipitation capacities (mg BSA precipitated/g dry wt) measured by the method for young and mature leaves of oaks were Quercus incana (young, 42.21; mature, 79.51), Q. ilex (young, 1.86; mature, 1.86), and Q. semecarpifolia (young, 733.54; mature, 304.32). The method can provide valuable information on the mechanisms of protein-tannin interactions and nutritional and physiological significances of tannins

Disposition of lantadene A, the pentacyclic triterpenoid hepatotoxin, orally administered to guinea pigs

Lantadene A (LA) administered orally to guinea pigs elicited cholestasis. LA could not be detected in liver, bile, gall bladder, blood and urine. LA and its biotransformation product reduced lantadene A (RLA) could be detected in caecum, large intestine, and faeces. In vitro incubation of LA with liver homogenates under aerobic and anaerobic conditions did not elicit its biotransformation to RLA. On the other hand, in vitro incubation of LA with guinea pig caecal and large intestinal contents under anaerobic conditions elicited conversion of LA to RLA. This is the first report of the biotransformation of LA in the animal system

A review of the noxious plant Lantana camara

O. P. Sharma, H. P. S. Makkar and R. K. Dawra. A review of the noxious plant Lantana camara. Toxicon 26, 975 – 987, 1988.— Lantana camara is one of the ten most noxious weeds in the world. It is toxic to animals and exerts allelopathic action on neighbouring vegetation. The pathological and biochemical effects of the lantana plant in cattle, sheep and guinea pigs have been determined. The chemical nature of lantana toxin(s) and the precise mechanism by which lantana induces cholestasis have not yet been defined clearly. Lantana toxicity is manifested in three phases: the release and absorption of toxins in the gastrointestinal tract; the hepatic phase resulting in cholestasis, hyperbilirubinaemia, hyperphylloerythrinaemia, and finally the tissue phase wherein cell injury results from the accumulation of bilirubin and phylloerythrin. Thus, therapeutic measures should be aimed at arresting one or more of these phases. The different means for control of lantana viz. mechanical, cultural, chemical and biological are discussed with regards to their effectiveness. A number of potential uses of lantana plant have been suggested but none has been exploited on a large scale. Future research is required in order to identify the lantana toxin, antidotes against lantana poisoning, cell - bilirubin/phylloerythrin interactions, cheaper weedicides, allelochemics and finally to obtain more effective phytophagous insects for fighting the lantana menace