Intraperitoneal Injection Of High Dose Research Articles

CU06-1004 alleviates oxidative stress and inflammation on folic acid-induced acute kidney injury in mice

PurposeAcute kidney injury (AKI) is characterized by reduced renal function, oxidative stress, inflammation, and renal fibrosis. CU06-1004, an endothelial cell dysfunction blocker, exhibits anti-inflammatory effects by reducing vascular permeability in pathological conditions. However, the potential effects of CU06-1004 on AKI have not been investigated. We investigated the renoprotective effect of CU06-1004 against oxidative stress, inflammation, and fibrotic changes in a folic acid-induced AKI model. MethodsAKI was induced by intraperitoneal injection of high dose (250 mg/kg) folic acid in mice. CU06-1004 was orally administered a low (10 mg/kg) or high dose (20 mg/kg). ResultsCU06-1004 ameliorated folic acid-induced AKI by decreasing serum blood urea nitrogen and creatinine levels, mitigating histological abnormalities, and decreasing tubular injury markers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in folic acid-induced AKI mice. Additionally, CU06-1004 alleviated folic acid-induced oxidative stress by reducing 4-hydroxynonenal and malondialdehyde levels. Furthermore, it attenuated macrophage infiltration and suppressed the expression of the proinflammatory factors, including tumor necrosis factor-α, intercellular adhesion molecule-1, and vascular cell adhesion protein-1. Moreover, CU06-1004 mitigated folic acid-induced tubulointerstitial fibrosis by decreasing α-smooth muscle actin and transforming growth factor-β expression. ConclusionThese findings suggest CU06-1004 as a potential therapeutic agent for folic acid-induced AKI.

Effects of Methamphetamine Exposure on Fear Learning and Memory in Adult and Adolescent Rats.

Methamphetamine (meth) use is often comorbid with anxiety disorders, with both conditions predominant during adolescence. Conditioned fear extinction is the most widely used model to study the fear learning and regulation that are relevant for anxiety disorders. The present study investigates how meth binge injections or meth self-administration affect subsequent fear conditioning, extinction and retrieval in adult and adolescent rats. In experiment 1, postnatal day 35 (P35-adolescent) and P70 (adult) rats were intraperitoneally injected with increasing doses of meth across 9days. At P50 or P85, they underwent fear conditioning followed by extinction and test. In experiments 2a-c, P35 or P70 rats self-administered meth for 11days then received fear conditioning at P50 or P85, followed by extinction and test. We observed that meth binge exposure caused a significant disruption of extinction retrieval in adult but not adolescent rats. Interestingly, meth self-administration in adolescence or adulthood disrupted acquisition of conditioned freezing in adulthood. Meth self-administration in adolescence did not affect conditioned freezing in adolescence. These results suggest that intraperitoneal injections of high doses of meth and meth self-administration have dissociated effects on fear conditioning and extinction during adulthood, while adolescent fear conditioning and extinction are unaffected.

Expression changes of hippocampal energy metabolism enzymes contribute to behavioural abnormalities during chronic morphine treatment

Dependence and impairment of learning and memory are two well-established features caused by abused drugs such as opioids. The hippocampus is an important region associated with both drug dependence and learning and memory. However, the molecular events in hippocampus following exposure to abused drugs such as opioids are not well understood. Here we examined the effect of chronic morphine treatment on hippocampal protein expression by proteomic analyses. We found that chronic exposure of mice to morphine for 10 days produced robust morphine withdrawal jumping and memory impairment, and also resulted in a significant downregulation of hippocampal protein levels of three metabolic enzymes, including Fe-S protein 1 of NADH dehydrogenase, dihydrolipoamide acetyltransferase or E2 component of the pyruvate dehydrogenase complex and lactate dehydrogenase 2. Further real-time quantitative PCR analyses confirmed that the levels of the corresponding mRNAs were also remarkably reduced. Consistent with these findings, lower ATP levels and an impaired ability to convert glucose into ATP were also observed in the hippocampus of chronically treated mice. Opioid antagonist naltrexone administrated concomitantly with morphine significantly suppressed morphine withdrawal jumping and reversed the downregulation of these proteins. Acute exposure to morphine also produced robust morphine withdrawal jumping and significant memory impairment, but failed to decrease the expression of these three proteins. Intrahippocampal injection of D-glucose before morphine administration significantly enhanced ATP levels and suppressed morphine withdrawal jumping and memory impairment in acute morphine-treated but not in chronic morphine-treated mice. Intraperitoneal injection of high dose of D-glucose shows a similar effect on morphine-induced withdrawal jumping as the central treatment. Taken together, our results suggest that reduced expression of the three metabolic enzymes in the hippocampus as a result of chronic morphine treatment contributes to the development of drug-induced symptoms such as morphine withdrawal jumping and memory impairment.

Haemodynamic and Exocrine Effects of Caerulein at Submaximal and Supramaximal Levels on the Rat Pancreas: Role of Cholecystokinin Receptor Subtypes

Background: We have investigated the involvement of cholecystokinin (CCK) receptor subtypes in haemodynamic changes in the pancreas of anaesthetized rats during submaximal and supramaximal stimulation with the CCK analogue, caerulein. Methods: For submaximal stimulation, caerulein (0.4 nmol/kg/h) was infused intravenously, while acute pancreatitis was induced by intraperitoneal injections of high doses of caerulein (3 × 25 nmol/kg). Pancreatic blood flow was measured by hydrogen clearance. Results: Low caerulein doses increased pancreatic blood flow by 26 ± 8% and vascular conductance by 24 ± 4%. This effect was mimicked by the CCK₂ agonist gastrin-17. All effects were abolished by a CCK₂ antagonist while a CCK₁ antagonist remained inactive. Conversely, amylase output by caerulein was abolished by CCK₁ receptor blockade, but not by inhibition of CCK₂ receptors. During caerulein-induced pancreatitis, vascular conductance increased by 109 ± 26% and remained elevated throughout the experiment; vascular flow initially increased by 62 ± 27% and then returned to baseline. The vascular effects were prevented by a CCK₂ receptor antagonist, while the induction of pancreatitis was due to CCK₁ receptor stimulation. Conclusions: Caerulein increases pancreatic vascular flow via activation of CCK₂ receptors. This effect occurs both at submaximal and at supramaximal levels of exocrine stimulation.

Proliferation of theileria annulata and Theileria parva macroschizont-infected bovine cells in scid mice

Theileria annulata and Theileria parva macroschizont-infected bovine cells formed tumours at the inoculation site when injected subcutaneously into C.B.-17 scid mice. T. annulata tumours showed more vigorous growth than T. parva tumours. The tumours did not regress and infected cells spread to other tissues. Intraperitoneal injection of high doses of T. annulata-infected cells resulted in the development of ascites; the infected cells colonized abdominal organs, in particular mesenteric tissue. Low doses of cells did not establish when administered by this route. Evidence for a role for macrophages in controlling proliferation of Theileria-infected cells was provided by finding (i) that uninfected bovine cells did not survive for as long in the peritoneal cavities of scid mice as in Balb/c mice; (ii) peritoneal macrophages both proliferated in vivo in the presence of infected cells and were activated as assessed by production of interleukin-1. Evidence against a role for NK cells was provided by (i) the failure of an in vivo assay for allogeneic lymphocyte cytotoxicity to reveal any activity against bovine cells in the lungs or liver, i.e. the sites usually associated with NK cell cytotoxicity, and (ii) the lack of correlation between tumour regression and NK cell activity in the spleens of mice with chronic T. annulata tumours.

The Use of 5 - Aminoimidazole-4-Carboxamide Riboside (AICA Riboside) to Improve Random Skin Flap Viability in the Rat Model

Several experimental studies have demonstrated that granulocytes have an important role in causing the necrosis of ischemic tissue by capillary plugging and superoxide radical formation. Adenosine is spontaneously released by ischemic cells and inhibits the granulocytic superoxide radical formation. 5-Aminoimidazole-4-carboxamide riboside, a naturally occurring by-product in purine biosynthesis, stimulates the release of ischemic cell adenosine and indirectly blocks the granulocyte-induced tissue necrosis. 5-Aminoimidazole-4-carboxamide riboside (10-500 mg/kg) was administered intraperitoneally in a blinded fashion once (single dose, 30 minutes before surgery) or twice (double dose, 30 minutes before and 5.5 hours after surgery) in groups of rats. The controls received intraperitoneal saline solution in the same fashion. Each rat underwent the elevation of a caudally based random skin flap. The flap viability was determined in a blinded fashion on the seventh post-operative day and statistically compared by Fisher's exact test. When 300 or 500 mg/kg of 5-aminoimidazole-4-carboxamide riboside was given as a single dose, the mean percentage of rat skin flap necrosis (19.4% +/- 3.1% and 19.6% +/- 4.2%, respectively) was lower but not significantly different from that of the control group of rats (29.3% +/- 2.7%) (p less than 0.08). Additionally, two doses of 500 mg/kg of 5-aminoimidazole-4-carboxamide riboside yielded a mean percentage of rat skin flap necrosis (12.24% +/- 4.58%) much lower (21.68% +/- 3.18%) than that of the control group of rats (p = 0.056). Our blinded fashion study demonstrated an almost statistically significant reduction of random skin flap distal necrosis after intraperitoneal injection of high doses of 5-aminoimidazole-4-carboxamide riboside.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereologic analysis of structures of the parenchyma and stroma of hypertrophied myocardium in acute arterial hypertension

It has been shown in experiments on Wistar male rats with the use of light and electron microscopy and morphometry that a single intraperitoneal injection of high doses of all-trans-methylretinoate and methyl-7,8- dihydroretinoate leads to an increase in the spleen weight, the appearance in the spleen of red cells changed in the shape, activation of phagocytic intensity of macrophages, intercellular interaction, lymphocyte proliferation and formation of new lymph follicles.

Cord factor not toxic in rats.

Systemic toxicity and local inflammatory activity of cord factor were compared between mice and rats. In mice, repeated intraperitoneal injection of cord factor caused a marked worsening of general condition and high mortality. The swelling of footpads injected with cord factor was also marked in mice. In contrast, injection of cord factor produced no such toxic reactions in rats, except that repeated intraperitoneal injections of high doses of cord factor induced an accumulation of ascites.