Pharmacological Reports最新文献

{"title":"Effect of bisphosphonates and statins on the in vitro radiosensitivity of breast cancer cell lines.","authors":"Larry Bodgi, Jolie Bou-Gharios, Joyce Azzi, Rafka Challita, Charbel Feghaly, Khanom Baalbaki, Hussein Kharroubi, Fatima Chhade, Fady Geara, Wassim Abou-Kheir, Zeina Ayoub","doi":"10.1007/s43440-023-00560-7","DOIUrl":"10.1007/s43440-023-00560-7","url":null,"abstract":"<p><strong>Background: </strong>Early-stage breast cancer is usually treated with breast-conserving surgery followed by adjuvant radiation therapy. Acute skin toxicity is a common radiation-induced side effect experienced by many patients. Recently, a combination of bisphosphonates (zoledronic acid) and statins (pravastatin), or ZOPRA, was shown to radio-protect normal tissues by enhancing DNA double-strand breaks (DSB) repair mechanism. However, there are no studies assessing the effect of ZOPRA on cancerous cells. The purpose of this study is to characterize the in vitro effect of the zoledronic acid (ZO), pravastatin (PRA), and ZOPRA treatment on the molecular and cellular radiosensitivity of breast cancer cell lines.</p><p><strong>Materials: </strong>Two breast cancer cell lines, MDA MB 231 and MCF-7, were tested. Cells were treated with different concentrations of pravastatin (PRA), zoledronate (ZO), as well as their ZOPRA combination, before irradiation. Anti-γH2AX and anti-pATM immunofluorescence were performed to study DNA DSB repair kinetics. MTT assay was performed to assess cell proliferation and viability, and flow cytometry was performed to analyze the effect of the drugs on the cell cycle distribution. The clonogenic assay was used to assess cell survival.</p><p><strong>Results: </strong>ZO, PRA, and ZOPRA treatments were shown to increase the residual number of γH2AX foci for both cell lines. ZOPRA treatment was also shown to reduce the activity of the ATM kinase in MCF-7. ZOPRA induced a significant decrease in cell survival for both cell lines.</p><p><strong>Conclusions: </strong>Our findings show that pretreatment with ZOPRA can decrease the radioresistance of breast cancer cells at the molecular and cellular levels. The fact that ZOPRA was previously shown to radioprotect normal tissues, makes it a good candidate to become a therapeutic window-widening drug.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of metformin on hypothalamic-pituitary-thyroid axis activity in women with autoimmune and non-autoimmune subclinical hypothyroidism: a pilot study.","authors":"Robert Krysiak, Karolina Kowalcze, Bogusław Okopień","doi":"10.1007/s43440-023-00556-3","DOIUrl":"10.1007/s43440-023-00556-3","url":null,"abstract":"<p><strong>Background: </strong>Metformin reduces plasma TSH levels if these levels are elevated. No study has investigated whether the hormonal effects of metformin are impacted by thyroid autoimmunity. The current study aimed to compare the effect of metformin on hypothalamic-pituitary-thyroid axis activity between subjects with mild hypothyroidism of different origins.</p><p><strong>Methods: </strong>The study population consisted of two groups of women with prediabetes and mildly elevated TSH levels, matched by age, insulin sensitivity, TSH, and thyroid hormone levels. Group A included 26 women with autoimmune thyroiditis, while group B enrolled 26 individuals with hypothyroidism of non-autoimmune origin. Both groups were treated with metformin (2.55-3 g daily). Circulating levels of TSH, total and free thyroid hormones, glucose, insulin, prolactin, high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D, concentrations of thyroid antibodies, and structure parameters of thyroid homeostasis were assessed at baseline and 6 months later.</p><p><strong>Results: </strong>All patients completed the study. At baseline, both groups differed in concentrations of thyroid peroxidase antibodies, thyroglobulin antibodies, hsCRP, and 25-hydroxyvitamin D. The drug reduced TSH and Jostel's index, with no difference between the study groups. The improvement in insulin sensitivity, observed in both groups, was more pronounced in group B than in group A. In women with autoimmune hypothyroidism, the drug increased SPINA-GT and decreased hsCRP levels. The remaining markers did not change throughout the study.</p><p><strong>Conclusions: </strong>The obtained results suggest that, despite differences in thyroid output, the impact of metformin on TSH levels is similar in hypothyroid women with and without thyroid autoimmunity.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of changes in the orexin system and energy sensors in the brain in depressive disorder - a study in an animal model.","authors":"Katarzyna Głombik, Magdalena Kukla-Bartoszek, Katarzyna Curzytek, Agnieszka Basta-Kaim, Bogusława Budziszewska","doi":"10.1007/s43440-023-00559-0","DOIUrl":"10.1007/s43440-023-00559-0","url":null,"abstract":"<p><strong>Background: </strong>Maternal elevated glucocorticoid levels during pregnancy can affect the developing fetus, permanently altering the structure and function of its brain throughout life. Excessive action of these hormones is known to contribute to psychiatric disorders, including depression.</p><p><strong>Materials: </strong>The study was performed in a rat model of depression based on prenatal administration of dexamethasone (DEX) in late pregnancy (0.1 mg/kg, days 14-21). We evaluated the effects of prenatal DEX treatment on the cognition and bioenergetic signaling pathways in the brain of adult male rats, in the frontal cortex and hippocampus, and in response to stress in adulthood, using behavioral and biochemical test batteries.</p><p><strong>Results: </strong>We revealed cognitive deficits in rats prenatally treated with DEX. At the molecular level, a decrease in the orexin A and orexin B levels and downregulation of the AMPK-SIRT1-PGC1α transduction pathway in the frontal cortex of these animals were observed. In the hippocampus, a decreased expression of orexin B was found and changes in the MR/GR ratio were demonstrated. Furthermore, an increase in HDAC5 level triggered by the prenatal DEX treatment in both brain structures and a decrease in MeCP2 level in the hippocampus were reported.</p><p><strong>Conclusions: </strong>Our study demonstrated that prenatal DEX treatment is associated with cognitive dysfunction and alterations in various proteins leading to metabolic changes in the frontal cortex, while in the hippocampus adaptation mechanisms were activated. The presented results imply that different pathophysiological metabolic processes may be involved in depression development, which may be useful in the search for novel therapies.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network analysis of monoamines involved in anxiety-like behavior in a rat model of osteoarthritis.","authors":"Jakub Mlost, Magdalena Białoń, Marta Kędziora, Agnieszka Wąsik, Żaneta Michalec, Katarzyna Starowicz","doi":"10.1007/s43440-023-00562-5","DOIUrl":"10.1007/s43440-023-00562-5","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain is a major health problem that affects a significant number of patients, resulting in personal suffering and substantial health care costs. One of the most commonly reported causal conditions is osteoarthritis (OA). In addition to sensory symptoms, chronic pain shares an inherent overlap with mood or anxiety disorders. The involvement of the frontal cortex, striatum and nucleus accumbens, in the affective processing of pain is still poorly understood.</p><p><strong>Methods: </strong>Male Wistar rats were divided into two groups: MIA (monoiodoacetate injected into the knee-model of OA) and sham (NaCl). Behavioral tests assessing pain, anxiety, and depressive behavior were performed at week 1, 3, 4, 6, 8, and 10. Neurochemical assays were conducted at weeks 3, 6, and 10 post-MIA injection, followed by the neurotransmitters and their metabolites correlation matrix and network analysis.</p><p><strong>Results: </strong>OA animals developed rapid pain phenotype, whereas anxiety-like behavior accompanied the development of a pain phenotype from 6 week post-MIA injection. We did not detect any depressive-like behavior. Instead, immobility time measured in the forced swimming test transiently decreased at 3 weeks post-MIA in the OA group. We detected changes in noradrenaline and serotonin levels in analyzed structures at distinct time points. Network analysis revealed noradrenaline and serotonin neurotransmission changes in the nucleus accumbens, confirming it to be the key structure affected by chronic pain.</p><p><strong>Conclusion: </strong>Animals with chronic pain exhibit symptoms of anxiety-like behavior and we identified underlying neurochemical changes using network analysis.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of non-standard regimen of systemic steroid therapy in patients with Graves' orbitopathy: a single-centre experience.","authors":"Nadia Sawicka-Gutaj, Dawid Gruszczyński, Natalia Zawalna, Kacper Nijakowski, Agnieszka Skiba, Mateusz Pochylski, Jerzy Sowiński, Marek Ruchała","doi":"10.1007/s43440-023-00567-0","DOIUrl":"10.1007/s43440-023-00567-0","url":null,"abstract":"<p><strong>Background: </strong>Graves' orbitopathy (GO) is an autoimmune disorder of the orbit and retro-ocular tissues and the primary extrathyroidal manifestation of Graves' disease. In moderate-to-severe and active GO iv glucocorticoids (GCs) are recommended as first-line treatment. The aim was to assess the safety profile of methylprednisolone administered intravenously for three consecutive days at 1 g in patients with active, moderate-to-severe or sight-threatening Graves' orbitopathy.</p><p><strong>Methods: </strong>We retrospectively evaluated 161 medical records of patients with GO treated with high-dose systemic GCs in the Department of Endocrinology, Metabolic Disorders, and Internal Medicine in Poznań between 2014 and 2021. Clinical data included age, gender, laboratory results, activity and severity of GO, smoking status, disease duration, and presented side effects.</p><p><strong>Results: </strong>The presence of mild side effects was observed during 114 (71%) hospitalizations. The most common complications were hyperglycemia (n = 95) and elevated aminotransferases (n = 31). Increased levels of aminotransferases were more likely observed in smokers and GO duration above 12 months. Based on the multivariate logistic regression, higher TRAb and CAS values were significantly associated with lower odds of hyperglycemia. In turn, the increased odds of elevated aminotransferases were significantly correlated with higher initial ALT levels, female gender, and GO duration above 12 months. In addition, the multidimensional correspondence analysis (MPA) showed that GO patients who declared smoking and had not L-ornithine L-aspartate applied demonstrated a higher probability of elevated aminotransferases.</p><p><strong>Conclusions: </strong>Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imperatorin interacts additively with novel antiseizure medications in the mouse maximal electroshock-induced seizure model: an isobolographic transformation.","authors":"Jarogniew J Łuszczki, Ewelina Kochman-Moskal, Hubert Bojar, Magdalena Florek-Łuszczki, Krystyna Skalicka-Woźniak","doi":"10.1007/s43440-023-00555-4","DOIUrl":"10.1007/s43440-023-00555-4","url":null,"abstract":"<p><strong>Background: </strong>Anticonvulsant effects of imperatorin (IMP) have been experimentally confirmed earlier, but no information is available on the interaction profiles of this naturally occurring coumarin when combined with novel antiseizure medication (ASMs). This study aimed to determine the effects of IMP on the anticonvulsant effects of lacosamide (LCM), oxcarbazepine (OXC), pregabalin (PGB), and topiramate (TPM) in the maximal electroshock-induced seizure (MES) model in mice.</p><p><strong>Methods: </strong>The anticonvulsant effects exerted by novel ASMs (LCM, OXC, PGB, and TPM) when combined with constant doses of IMP (25 and 50 mg/kg) underwent isobolographic transformation to precisely classify the observed interactions in the mouse MES model. Total brain concentrations of ASMs were measured with high-pressure liquid chromatography to exclude the pharmacokinetic nature of interactions among IMP and the tested ASMs.</p><p><strong>Results: </strong>IMP (50 mg/kg) significantly enhanced (p < 0.01) the anticonvulsant potency of LCM, OXC, PGB, and TPM in the mouse MES model. IMP (25 mg/kg) mildly potentiated the anticonvulsant action of LCM, OXC, PGB, and TPM, but no statistical significance was reported for these combinations. The isobolographic transformation of data from the MES test revealed that the interactions of novel ASMs with IMP were additive. Moreover, IMP (50 mg/kg) did not affect the total brain content of any of the novel ASMs in experimental mice.</p><p><strong>Conclusions: </strong>The additive interactions of IMP with LCM, OXC, PGB, and TPM in the mouse MES model accompanied by no pharmacokinetic changes in the total brain content of ASMs are worthy of recommendation for further studies.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid-lowering drugs and cancer: an updated perspective.","authors":"Azin Alizadehasl, Maryam Sadat Alavi, Shabnam Boudagh, Mohaddeseh Sadat Alavi, Somaye Mohebi, Leila Aliabadi, Mahsa Akbarian, Parisa Ahmadi, Massimo R Mannarino, Amirhossein Sahebkar","doi":"10.1007/s43440-023-00553-6","DOIUrl":"10.1007/s43440-023-00553-6","url":null,"abstract":"<p><p>Statins and non-statin medications used for the management of dyslipidemia have been shown to possess antitumor properties. Since the use of these drugs has steadily increased over the past decades, more knowledge is required about their relationship with cancer. Lipid-lowering agents are heterogeneous compounds; therefore, it remains to be revealed whether anticancer potential is a class effect or related to them all. Here, we reviewed the literature on the influence of lipid-lowering medications on various types of cancer during development or metastasis. We also elaborated on the underlying mechanisms associated with the anticancer effects of antihyperlipidemic agents by linking the reported in vivo and in vitro studies.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weighted gene co-expression network analysis for hub genes in colorectal cancer.","authors":"Zheng Xu, Jianing Wang, Guosheng Wang","doi":"10.1007/s43440-023-00561-6","DOIUrl":"10.1007/s43440-023-00561-6","url":null,"abstract":"<p><strong>Background: </strong>This study is designed to explore hub genes participating in colorectal cancer (CRC) development through weighted gene co-expression network analysis (WGCNA).</p><p><strong>Methods: </strong>Expression profiles of CRC and normal samples were retrieved from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA), and were subjected to WGCNA to filter differentially expressed genes with significant association with CRC. Functional enrichment analysis and protein-protein interaction (PPI) analysis were carried out to filter the candidate genes, further and survival analysis was performed for the candidate genes to obtain potential regulatory hub genes in CRC. Expression analysis was conducted for the candidate genes and a multifactor model was established.</p><p><strong>Results: </strong>After differential analysis and WGCNA, 289 candidate genes were filtered from the GEO and TCGA. Further functional enrichment analysis demonstrated possible regulatory pathways and functions. PPI analysis filtered 15 hub genes and survival analysis indicated a significant correlation of CLCA1, CLCA4, and CPT1A with prognosis of patients with CRC. The multifactor Cox risk model established based on the three genes revealed that if the three genes were a gene set, they had well predictive capacity for the prognosis of patients with CRC.</p><p><strong>Conclusions: </strong>CLCA1, CLCA4, and CPT1A express at low levels in CRC and function as core anti-tumor genes. As a gene set, they can predict prognosis well.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of brivaracetam on cognitive processes and anxiety in various experimental models.","authors":"Ewa Zwierzyńska, Bogusława Pietrzak","doi":"10.1007/s43440-023-00564-3","DOIUrl":"10.1007/s43440-023-00564-3","url":null,"abstract":"<p><strong>Background: </strong>Memory deficits and anxiety symptoms are undesirable effects that occur in epilepsy patients. They may be associated with the pathophysiology of the disease but also with anticonvulsant therapy. Brivaracetam (BRV) is one of the newest antiseizure drugs. It acts as a ligand for synaptic vesicle glycoprotein 2A (SV2A), which may play a significant role in cognitive processes. Although BRV has a favorable safety profile, its central side effects remain unclear. Hence, this study aimed to evaluate the effect of BRV on various types of memory and anxiety in rats.</p><p><strong>Methods: </strong>BRV was given to adult male Wistar rats (n = 80) via gastric tube as a single dose (6 mg/kg or 20 mg/kg) or chronically (6 mg/kg). The effect of the drug on spatial memory was evaluated in the Morris water maze (MWM), fear-learning by passive avoidance (PA), and recognition memory with novel object recognition (NOR). The elevated plus maze (EPM) was used to assess anxiety-like behaviors.</p><p><strong>Results: </strong>The impact of BRV on memory is dose-dependent and mainly high doses may alter retrieval memory and fear-learning. Sub-chronic administration also impaired retrieval and spatial memory in animals. Moreover, chronic BRV may increase anxiety levels in rats but did not affect recognition memory.</p><p><strong>Conclusions: </strong>BRV may cause transient memory deficits as well as anxiety disturbances. However, the results are varied and depend on the type of memory, used dose, and duration of administration.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139106494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reno-protective effect of protocatechuic acid is independent of sex-related differences in murine model of UUO-induced kidney injury.","authors":"Karim M Saad, Évila Lopes Salles, Sahar Emami Naeini, Babak Baban, Marwa E Abdelmageed, Rania R Abdelaziz, Ghada M Suddek, Ahmed A Elmarakby","doi":"10.1007/s43440-023-00565-2","DOIUrl":"10.1007/s43440-023-00565-2","url":null,"abstract":"<p><strong>Background: </strong>Obstructive nephropathy is a condition often caused by urinary tract obstruction either anatomical (e.g., tumors), mechanical (e.g., urolithiasis), or compression (e.g., pregnancy) and can progress to chronic kidney disease (CKD). Studies have shown sexual dimorphism in CKD, where males were found to have a more rapid decline in kidney function following kidney injury compared to age-matched females. Protocatechuic acid (PCA), an anti-oxidant and anti-inflammatory polyphenolic compound, has demonstrated promising effects in mitigating drug-induced kidney injuries. The current study aims to explore sexual dimorphism in kidney injury after unilateral ureteral obstruction (UUO) and assess whether PCA treatment can mitigate kidney injury in both sexes.</p><p><strong>Methods: </strong>UUO was induced in 10-12 weeks old male and female C57BL/6J mice. Mice were categorized into four groups (n = 6-8/group); Sham, Sham plus PCA (100 mg/kg, I.P daily), UUO, and UUO plus PCA.</p><p><strong>Results: </strong>After 2 weeks of induction of UUO, markers of kidney oxidative stress (TBARs), inflammation (IL-1α and IL-6), tubular injury (neutrophil gelatinase-associated lipocalin, NGAL and urinary kidney injury molecule-1, KIM-1), fibrosis (Masson's trichrome staining, collagen IV expression, MMP-2 and MMP-9) and apoptosis (TUNEL⁺ cells, active caspase-1 and caspase-3) were significantly elevated in both males and females relative to their sham counterparts. Males exhibited significantly greater kidney oxidative stress, inflammation, fibrosis, and apoptosis after induction of UUO when compared to females. PCA treatment significantly attenuated UUO-induced kidney injury, inflammation, fibrosis, and apoptosis in both sexes.</p><p><strong>Conclusion: </strong>Our findings suggest a differential gender response to UUO-induced kidney injury with males being more sensitive to UUO-induced kidney inflammation, fibrosis, and apoptosis than age-matched females. Importantly, PCA treatment reduced UUO-induced kidney injury in a sex-independent manner which might be attributed to its anti-oxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic properties.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139425265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}