Introduction/Background

Parkinson’s disease, the second most common neurodegenerative disease, is still lacking an effective treatment that can stop dopaminergic cell loss in substantia nigra and alter disease progression. The present study aimed to investigate the neuroprotective efficacy of lithium chloride in a rotenone-induced rat model of Parkinson’s disease.

Methods

Forty male Sprague Dawley rats were assigned into 4 groups: control, rotenone-, rotenone and lithium chloride- and lithium chloride-treated groups. Rotenone (2 mg/kg b.w.) and lithium chloride (60 mg/kg b.w.) were, respectively, administered subcutaneously and orally five times a week for 5 weeks. At the end of each treatment, the neuroprotective efficacy of lithium chloride against rotenone-induced derangements was evaluated by some behavioral tests, biochemical analysis, gel electrophoresis, histopathology, and immunohistochemistry.

Results

Rotenone significantly resulted in neurobehavioral deficits, gastrointestinal dysfunction, decreased activities of catalase and superoxide dismutase, depleted glutathione, and increased levels of malondialdehyde. It also caused DNA fragmentation and loss of dopaminergic neurons in substantia nigra and decreased striatal tyrosine hydroxylase staining intensity. Concomitant treatment of rats with rotenone and lithium chloride significantly improved behavioral impairment and markedly alleviated gastrointestinal dysfunction. It also increased catalase activity and decreased malondialdehyde levels, indicating antioxidant effects. Moreover, it decreased DNA fragmentation, rescued dopaminergic neurons, and increased tyrosine hydroxylase immunoreactivity in the striatum compared to the rotenone-treated group.

Conclusion

Lithium chloride rescued dopaminergic neurons in a rotenone model of PD, possibly through the improvement of behavioral deficits, decreasing oxidative stress, and reducing DNA damage.

Background: Chronic inflammation and immune dysregulation are key drivers of diabetes complications. Rivaroxaban (RX) and sitagliptin (SITA) are established therapies for thromboembolism and glycemic control, respectively. This study evaluated the novel therapeutic potential of nano-rivaroxaban (NRX) alone and in combination with sitagliptin (SITA) in mitigating inflammation and restoring immune balance in streptozotocin (STZ)-induced diabetic rats. Methods: Type 2 diabetes was induced in rats using a single injection of STZ (60 mg/kg). Animals were divided into five groups: control, STZ-diabetic, RX-treated (5 mg/kg), NRX-treated (5 mg/kg), and NRX+SITA-treated (5 mg/kg + 10 mg/kg). After 4 weeks of treatment, blood glucose, coagulation markers, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and anti-inflammatory cytokines (IL-35, TGF-β1, IL-10) were analyzed. Histopathological examination of the liver, kidney, pancreas, and spleen was conducted. Immunohistochemistry was used to assess hepatic NF-κB expression. Results: STZ significantly elevated pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and anti-inflammatory cytokines (IL-35, TGF-β1, IL-10), along with increased hepatic NF-κB expression and histopathological abnormalities in immune organs. NRX significantly reduced inflammatory cytokines, improved histopathological changes in organs, and decreased hepatic NF-κB expression. The combination therapy (NRX + SITA) achieved superior immune modulation, with enhanced cytokine profile restoration, reduced hepatic NF-κB expression, and near-complete histopathological normalization. Conclusions: This study underscores the promise of combining nanoparticle-based drug delivery with established therapies like sitagliptin to achieve superior immune modulation and inflammation control, presenting a potential therapeutic strategy for managing diabetes complications.

Doxorubicin (DOX) is a commonly used chemotherapeutic medication for treating malignancies, although its cardiotoxicity limits its use. There is growing evidence that alteration of the mitochondrial fission/fusion dynamic processes accompanied by excessive reactive oxygen species (ROS) production and alteration of calcium Ca²⁺ homeostasis are potential underlying mechanisms of DOX-induced cardiotoxicity (DIC). Metformin (Met) is an AMP-activated protein kinase (AMPK) activator that has antioxidant properties and cardioprotective effects. The purpose of the study is to assess Met's possible cardioprotective benefits against DOX-induced cardiotoxicity. The study included 32 adult male rats. They were randomly divided into four groups: administered saline, DOX, Met, or DOX combined with Met respectively. Heart tissues were used for biochemical assays that measured oxidative stress markers, malondialdehyde (MDA), reduced glutathione (GSH), mitochondrial dynamics markers, optic atrophy-1(OPA-1) and dynamin-1-like protein (Drp1), calcineurin and caspase-3. Serum levels of myocardial injury markers, cardiac troponin I (cTn-I), and aspartate aminotransferase (AST), were also measured. The results revealed that DOX intoxication was associated with a significant increase in the levels of serum cTn-I and AST, increased cardiac MDA level, increased cardiac Drp1, calcineurin, and caspase-3 expressions, as well as reduced cardiac GSH level and cardiac OPA-1 expression. On the other hand, Met treatment significantly reduced DIC by decreasing oxidative stress, apoptosis, and improving mitochondrial and calcium balance. Finally, this study shows that Met may be able to protect the heart from damage caused by DOX by working as an antioxidant and anti-apoptotic agent and keeping the balance of calcium and mitochondria.

Acute renal failure (ARF) is a sudden, significant, and often reversible decline in kidney function, with 25% of all hospital-administered pharmaceuticals potentially causing nephrotoxicity. The study investigates the effectiveness of a novel nanoparticle (NP) formulation of glutathione (GSH) and Lepidium sativum (LS) in improving therapeutic outcomes in a rat model of ARF. Sixty adult male albino rats were allocated into ten groups, comprising six rats each, for the study. ARF was created by daily gentamicin (GN) administration for seven consecutive days and various treatment protocols, including chitosan (CS) NPs, spanlastics NPs, as well as conventional, NP formulations of GSH, LS, and their respective combinations. The effect was evaluated through various tests, and properties of nanoparticles were confirmed through characterization processes. The NP compositions markedly enhanced renal function, as seen by reduced urine concentrations of albumin and glucose. Furthermore, the serum concentrations of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C were decreased. Tissue concentrations of nitrite, superoxide dismutase (SOD), and malondialdehyde (MDA), as markers of oxidative stress, were enhanced by both conventional and NP formulations. Additionally, they decreased inflammatory markers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Histological analysis and immunohistochemical testing revealed that the combination therapy, particularly with the nanoforms, significantly decreased caspase 3 cellular immunoexpression, a sign of kidney cellular damage. The findings show that the ARF renal damage is considerably reduced when NPs containing GSH and LS are administered together. The study suggests a promising pharmacological approach for enhancing kidney regeneration and preserving renal function, potentially aiding in new therapeutic interventions for ARF treatment.

Purpose

A multitude of inflammatory cells and chemical mediators initiate a complex cascade that ultimately leads to hepatocyte death and a systemic inflammatory response. This research aimed to investigate the potential effects of sildenafil and neem (Azadirachta indica) extract, in both conventional and nanoparticle (NP) forms, in the treatment of moderate acute liver damage induced by orogastric carbon tetrachloride (CCL₄).

Methods

To induce moderate acute hepatic damage a single oral dosage of CCL₄ (2.5 mL/kg body weight) was provided 24 h before euthanasia. In liver damage-induced CCL₄, sildenafil and neem extract were given in conventional and nanoparticle (PLGA or niosome) forms. To find histological anomalies and hepatic changes, behavioral, biochemical, histopathological, and immunohistochemical methods were used.

Results

The findings indicated that sildenafil and/or neem extract, especially in NP combination, significantly mitigated CCL₄-induced acute moderate liver damage. Indicators of liver function, including aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), albumin, bilirubin and gamma-glutamyl transferase (GGT), shown improvement, particularly with the nanoparticulation of both therapies. Treatment, particularly in NP forms, improved the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase activity (GPx) in liver tissues. A significant reduction in NF-κB expression in hepatic tissue was shown in treatment groups. Also, medication resulted in lower levels of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), caspase-3, and transforming growth factor-beta (TGF-β) in the liver tissue homogenates. Liver function was more significantly improved by the drug-NP combination.

Conclusions

This study verified the beneficial therapeutic effects of the combination of sildenafil and neem extract, particularly in NP forms, using biochemical, histological, and immunohistochemical analyses in a rat model of liver damage.

    This study examines the development of the rabbit cerebellum from the 10th day postconception to full-term fetal age, with a particular focus on the role of radial glial cells in the differentiation of cerebellar neurons. A total of 35 embryonic samples were meticulously dissected and microscopically analyzed. On embryonic day (ED) 12, cerebellar primordia, consisting of the ventricular neuroepithelium and rhombic lip, were observed. By ED16, significant neuronal cell proliferation and migration in both the radial and tangential directions were noted. On ED 20, lamination processes began, forming the external granular layer (EGL) and Purkinje cell plate (PCP) with the support of radial glial cells. By ED 25, the cerebellar cortex had developed three distinct layers: the EGL, PCP, and the prospective molecular layer (PML), with radial glial cells localized in the PCP. Differentiation continued, and upon ED30, a new cortical layer, the internal granular layer, was evident. Additionally, the gradual replacement of nestin by glial fibrillary acidic protein marked the differentiation of radial glia into Bergmann glia at ED 25 and ED 30. β-III tubulin, a marker of differentiated neurons, was detected in the inner layer of EGL and PCP during these stages. In conclusion, this study highlights the pivotal role of radial glial cells in the layered organization and neuronal differentiation of the developing rabbit cerebellum. The developmental trajectory observed provides valuable insights into cerebellar morphogenesis and supports the relevance of the rabbit model for exploring neurodevelopmental processes.

Unlike mammals, species such as fish and amphibians can regenerate damaged spinal
cords, offering insights into potential therapeutic targets. This study investigates the
structural features of the molly fish spinal cord through light and electron microscopy.
The most notable characteristic was the presence of Mauthner cells (M-cells), which
exhibited large cell bodies and processes, as well as synaptic connections with astrocytes. These astrocytic connections contained synaptic vesicles, suggesting electrical
transmission at the M-cell endings. Astrocytes, which were labeled with glial fibrillary
acidic protein (GFAP), contained cytoplasmic glycogen granules, potentially serving as
an emergency fuel source. Two types of oligodendrocytes were identified: a small,
dark cell and a larger, lighter cell, both of which reacted strongly with oligodendrocyte
transcription factor 2 (Olig2). The dark oligodendrocyte resembled human oligodendrocyte precursors, while the light oligodendrocyte was similar to mature human oligodendrocytes. Additionally, proliferative neurons in the substantia grisea centralis
expressed myostatin, Nrf2, and Sox9. Collectively, these findings suggest that the
molly fish spinal cord has advanced structural features conducive to spinal cord
regeneration and could serve as an excellent model for studying central nervous system regeneration. Further studies on the functional aspects of the molly fish spinal
cord are recommended.
 

Fish ovaries exhibit a remarkable diversity in
shape, size, and organization, reflecting the myriad
reproductive strategies employed by different species.
This review delves into the intricate biology of fish
ovaries, highlighting their structural diversity and the
hormonal regulation that governs ovarian development
and oocyte maturation. Key hormones include pituitary
gonadotropins (GTHs) and maturation-inducing
hormones (MIHs), which initiate oocyte growth and
maturation. GTHs stimulate ovarian production of
estradiol-17β and 17α,20β-DP, which induce oocyte
maturation via MPF formation. Sex steroids like
estrogens and progestogens, synthesized from
cholesterol, play crucial roles. Other hormones,
including growth hormone, prolactin, thyroid hormones,
IGFs, ACTH, and melatonin, influence ovarian activity.
The review also explores the varied reproductive
strategies among fish, including oviparity and viviparity,
and discusses how environmental factors like water
temperature and photoperiod influence ovarian
histology. Understanding the complex interplay between
these factors is essential for advancing fisheries
management, conservation, and aquaculture practices.
Additionally, the evolutionary trajectory of fish ovaries
underscores their adaptation to diverse ecological niches,
contributing to the survival and reproductive success of
fish species. The ovarian stroma provides structural
support and houses various cell types, including
dendritic cells (DCs), endocrine cells, and telocytes,
contributing to follicle growth and hormone production,
essential for reproductive success in fish. Fish ovaries
are a crucial aspect of fish biology, with their structure
and function intricately regulated by hormonal,
environmental, and seasonal factors.
 

The structure of photoreceptors (PR) and the arrangement of neurons in the retina of
red-tail shark were investigated using light and electron microscopy. The PR showed
a mosaic arrangement and included double cones, single cones (SC), and single rods.
Most cones occur as SC. The ratio between the number of cones and rods was
3:1.39 (±0.29). The rods were tall that reached the pigmented epithelium. The outer
plexiform layer (OPL) showed a complex synaptic connection between the horizontal
and photoreceptor terminals that were surrounded by Müller cell processes. Electron
microscopy showed that the OPL possessed both cone pedicles and rod spherules.
Each rod spherule consisted of a single synaptic ribbon within the invaginating terminal endings of the horizontal cell (hc) processes. In contrast, the cone pedicles possessed many synaptic ribbons within their junctional complexes. The inner nuclear
layer consisted of bipolar, amacrine, Müller cells, and hc. Müller cells possessed intermediate filaments and cell processes that can reach the outer limiting membrane and
form connections with each other by desmosomes. The ganglion cells were large multipolar cells with a spherical nucleus and Nissl’ bodies in their cytoplasm. The presence of different types of cones arranged in a mosaic pattern in the retina of this
species favors the spatial resolution of visual objects.