• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.4
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• pp.347-350
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• 2018

Drug-induced autoimmune hepatitis (DIAIH) is an increasingly recognized form of drug-induced liver injury that leads to a condition similar to idiopathic autoimmune hepatitis. A number of drugs have been associated with DIAIH, minocycline is one of the most well characterized. Minocycline is a semisynthetic tetracycline antibiotic used in the treatment of acne vulgaris. Minocycline-induced autoimmune hepatitis presents with serologic and histologic features similar to idiopathic autoimmune hepatitis. However, the natural history and outcomes of these two conditions differ significantly. The majority of patients with minocycline-induced autoimmune hepatitis experience complete resolution of symptoms after withdrawal of the medication. Some patients may require a short course of steroids and rarely use of an immunomodulator to achieve resolution of disease. Recurrence of symptoms is rare and typically only occurs with reintroduction of minocycline. It is important for primary care providers to consider minocycline-induced autoimmune hepatitis when liver injury develops during minocycline therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.5
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• pp.237-243
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• 2004

Glial cells are activated in neuropathy and play a key role in hyperalgesia and allodynia. This study was performed to determine whether minocycline could attenuate heat hyperalgesia and mechanical allodynia, and how glial cell activation and nuclear factor kappa B (NF-kappaB) were regulated by minocycline in a model of chronic constriction of sciatic nerve (CCl). When minocycline (50 mg/kg, oral) was daily administered from 1 day before to 9 days after ligation, heat hyperalgesia and mechanical allodynia were attenuated. Furthermore, when minocycline treatment was initiated 1 or 3 days after ligation, attenuation of the hypersensitive behavior was still robust. However, the effect of attenuation was less when minocycline was started from day 5. In order to elucidate the mechanism of pain attenuation by minocycline, we examined the changes of glia and NF-kappaB, and found that attenuated hyperalgesia and allodynia by minocycline was accompanied by reduced microglial activation. Furthermore, the number of NF-kappaB immunoreactive cells increased after CCI treatment and this increase was attenuated by minocycline. We also observed translocation of NF-kappaB into the nuclei of activated glial cells. These results suggest that minocycline inhibits activation of glial cells and NF-kappaB, thereby attenuating the development of behavioral hypersensitivity to stimuli.

• Journal of Periodontal and Implant Science
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• v.28 no.1
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• pp.37-56
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• 1998

The purpose of this study was to evaluate the clinical and microbiological outcomes following the use of 30% minocycline-loaded polycaprolacton film and 2% minocycline-loaded gel that was applied locally into pockets combined with scaling and root planing. 25 human subjects who were non-pregnant, non-lactating, aged 20-50 and diagnosed as moderate to advanced adult periodontitis were enrolled. Subjects were excluded if they had a history of severe acute or chronic systemic disease, if they required antibiotic prophylaxis for dental treatment for any reason, or if they reported a history suggestive of hypersensitivity reactions to minocycline or tetracycline. 4quadrants that had several teeth with a 5-8mm probing pocket depth and radiographic evidence of alveolar bone loss for each patient were selected and divided into test sites and control sites according to the split-mouth design. Scaling and root planing was done for each site at baseline(0week). Test sites received the minocycline gel and strip and control sites had saline irrigation. The patients received both treatments simyltaneously. Subgingival irrigation of sterile saline was applied to the control sites for approximately 30 seconds. Minocycline strip and gel was applied into the periodontal pocket at 1, 2, 3, 4 weeks each after scaling and root planing in the test sites. The clinical and microbiological measurements were made at baseline and at the follow-up visits 6, 10, 14, 20 weeks. The results of this study were as follows; 1. The sulcular bleeding index, probing pocket depth and Periocheck test was significantly reduced and the relative proportions of spirochetes and motile rods were significantly reduced and the proportion of cocci was correspondingly increased, in locally delivered minocycline strip group compared to saline irrigation group. 2. In locally delivered minocycline gel group, The effect was the same with minocycline strip group as compared with saline irrigation therapy. 3. There was no significant differences between minocycline strip group and minocycline gelgroup. In conclusion, minocycline HCl local drug delivery combined with scaling and root planing may provide added improvement of clinical and microbiological responses by inhibiting bacterial recolonization of treated sites. It is suggested that the local administration of minocycline-HCl in the periodontal pocket is effective when combined with subgingival mechanical debridement.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.25 no.4
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• pp.304-310
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• 1999

This study was designed to find the effect of Minocycline loaded microcapsule applied locally to tissue by measuring drug concentration in tissue and serum by HPLC and to achieve optimal drug delivery system and duration to a specific target site. Control group were administrated minocycline intramuscularly twice a day with $0.2{\mu}g/100g$ for 1 to 10 days. In experimental group, surgical wound was created on Rt. cheek and then minocycline loaded microcapsule was applied into the space between superficial and deep layer of masseter muscle. Animals were sacrificed at 1, 3, 5, 7, 10 days after initial administration, blood was obtained from heart and right masseter muscle was excised. Blood sample was centrifuged at 3000rpm for 15min. Tissue sample was homogenized, left at room temperature for 48hr and centrifuged at 4000g for 5min. Supernatant was completely dried and dissolved in distilled water. Analysis was conducted using a ${\mu}Bondapack$ C18 column. The mobile phase was 0.2M Ammonium Oxalate/0.1M EDTA/DMF=11/4/5 solution, which was injected into the column and detected with photodiode detector at 344nm wavelength. The results were as follows : 1. This method was reliable, could be replicated and suitable for minocycline analysis in tissue as well as serum. 2. In tissue, concentration of minocycline of experimental group was higher than that of control group for 5days. 3. Except 1 day, concentration of minocycline in serum of experimental group was lower than that of control group. 4. Concentration of minocycline in tissue was much higher than that in serum. From these results, minocycline loaded microcapsule might be effective tool for local drug delivery system might be useful for treatment of infections of oral and maxillofacial region and management of infected surgical wound, minimizing systemic effects.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.67-67
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• 2003

Minocycline is known to protect neurons from microglia-mediated cell death in many experimental models of brain diseases including ischemic stroke, Huntingtons disease (HD), amyotrophic lateral sclerosis (ALS), traumatic brain injury, multiple sclerosis, and Parkinsons disease. When the activity of caspases was assessed using their fluorescent peptide substrates, activation of caspase-2, 3, 8, and 9 was evident within 2 8 hr following oxidative insult with 0.5 mM hydrogen peroxide in PC12 cells. Minocycline significantly attenuated activation of these caspases up to 18 hr, resulting a significant increase in the cell viability as assessed by MTT assay as well as trypan blue staining. However, cleavage of alpha-spectrin and a cdk5 activator p35, which are known to be substrates for calpain, remained unchanged in the presence of minocycline, suggesting that minocycline did not block caspase-3-independent cell death or necrosis. Moreover, co-treatment with minocycline and a calpain inhibitor calpeptin synergistically inhibited hydrogen peroxide-induced cell death. These data suggest that minocycline directly inhibited apoptosis, but not necrosis, after oxidative insult in PC12 cells.

• Archives of Pharmacal Research
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• v.27 no.3
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• pp.314-318
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• 2004

Microglia are the major inflammatory cells in the central nervous system and become activated in response to brain injuries such as ischemia, trauma, and neurodegenerative diseases including Alzheimer's disease (AD). Moreover, activated microglia are known to release a variety of proinflammatory cytokines and oxidants such as nitric oxide (NO). Minocycline is a semi-synthetic second-generation tetracycline that exerts anti-inflammatory effects that are completely distinct form its antimicrobial action. In this study, the inhibitory effects of minocycline on NO and prostaglandin E$_2$ (PGE$_2$) release was examined in lipopolysaccharides (LPS)-challenged BV2 murine microglial cells. Further, effects of minocycline on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels were also determined. The results showed that minocycline significantly inhibited NO and PGE$_2$ production and iNOS and COX-2 expression in BV2 microglial cells. These findings suggest that minocycline should be evaluated as potential therapeutic agent for various pathological conditions due to the excessive activation of microglia.

• Journal of Pharmaceutical Investigation
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• v.21 no.4
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• pp.247-251
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• 1991

Effects of aluminum magnesium hydroxide (A) and cimetidine (C) on the pharmacokinetics of minocycline (M) were investigated in female rats. Blood samples were collected at various time intervals until 36 hrs following oral dosing of drugs. Plasma minocycline concentrations were determined by HPLC. Control group (M), $T_1$ group (M+A), $T_2$ group (A+M after 2 hrs), $T_3$ group (M+A after 2 hrs), $T_4$ group (M+C) and $T_5$ group (C+M after 2 hrs) were divided to examine interaction of the drugs with minocycline. Plasma minocyline level-time curves were well described by two-compartment open model with first-order absorption in rats. Antacid treatment was associated with reduced of 71.0, 45.9, 35.7% in minocycline absorption rate $constant(K_{\alpha})$, maximum plasma $concentration(C_{max})$, and relative $bioavailability(F_{rel})$, respectively. Cimetidine treatment group exhibited no significant changes in plasma level-time curve when compared with control group and did not affect minocycline absorption as by any of these three parameters.

• Journal of Veterinary Clinics
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• v.34 no.2
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• pp.119-122
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• 2017

Calcinosis cutis is a chronic condition characterized by insoluble calcified deposits in the skin and subcutaneous tissue. Although there is no uniformly effective treatment for calcinosis cutis, minocycline therapy has demonstrated varying degrees of benefit in humans. Five client-owned dogs with calcinosis cutis were included. Minocycline was administered orally in a dose of 10 mg/kg bodyweight twice a day. Treatment was repeated every day until complete remission. The efficacy of minocycline was evaluated within this period. The side effects of minocycline were monitored and reported by the owners and veterinarians. Of the 5 dogs with calcinosis cutis, which was classified as the dystrophic form, four dogs had a complete remission of calcinosis cutis and one dog had a partial response. The major improvement was a reduction in the size of the calcified deposits and reduction in inflammation associated with them. The duration of remission was $9.1{\pm}2.2$ weeks. The adverse effects, observed in one dog, were anorexia and vomiting. Minocycline may be effective in the control of calcinosis cutis in dogs.

• Journal of Korean Neurosurgical Society
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• v.49 no.2
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• pp.83-91
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• 2011

Objective : Minocycline, a second-generation tetracycline-class antibiotic, has been well established to exert a neuroprotective effect in animal models and neurodegenerative disease through the inhibition of microglia. Here, we investigated the effects of minocycline on motor recovery and neuropathic pain in a rat model of spinal cord injury. Methods : To simulate spinal cord injury, the rats' spinal cords were hemisected at the 10th thoracic level (T10). Minocycline was injected intraperitoneally, and was administered 30 minutes prior surgery and every second postoperative day until sacrifice 28 days after surgery. Motor recovery was assessed via the Basso-Beattie-Bresnahan test Mechanical hyperalgesia was measured throughout the 28-day post -operative course via the von Frey test Microglial and astrocyte activation was assessed by immunohistochemical staining for ionized calcium binding adaptor molecule 1 (lba1) and glial fibrillary acidic protein (GFAP) at two sites: at the level of hemisection and at the 5th lumbar level (L5). Results : In rats, spinal cord hemisection reduced locomotor function and induced a mechanical hyperalgesia of the ipsilateral hind limb. The expression of lba1 and GFAP was also increased in the dorsal and ventral horns of the spinal cord at the site of hemisection and at the L5 level. Intraperitoneal injection of minocycline facilitated overall motor recovery and attenuated mechanical hyperalgesia. The expression of lba1 and GFAP in the spinal cord was also reduced in rats treated with minocycline. Conclusion : By inhibiting microglia and astrocyte activation, minocycline may facilitate motor recovery and attenuate mechanical hyperalgesia in individuals with spinal cord injuries.

• Journal of Periodontal and Implant Science
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• v.26 no.1
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• pp.188-201
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• 1996

One of the initial events required for periodontal regeneration is the attachment, spreading and proliferation of fibroblasts at the healing sites. These have been reported that minocycline stimulates the attachment of gingival fibroblasts and periodontal ligament cells and $TGF-{\beta}1$ enhances the proliferation of periodontal ligament cells. The purpose of this study was to evaluate and confirm the effect of minocycline and $TGF-{\beta}1$ on human gingival fibroblasts and periodontal ligament cells. That gingival fibroblasts and periodontal ligament cells used in this study were obtained from the explants of healthy periodontal ligaments and gingival tissues of extracted 3rd molars or premolar teeth extracted from the patients with orthodontic treatment. The cells were cultured in ${\alpha}-MEM$(minimal essential medium) supplemented with antibiotics and FBS(fetal bovine serum) at $37^{\circ}C$ in a humidified atmosphere of 5% carbon dioxide-95% air. Cells were used between the 5th to 8th passage in this study. The attachment and activity of both cells were evaluated by MTT assay. The results were as follows: 1. Maximum gingival fibroblast attachment was seen at a $50{\mu}g/ml$ dose of minocycline, while maximum periodontal ligament cell attachment was seen at a $100{\mu}g/ml$, and exposure of both cells to minocycline above maximal attachment dose results in a decline from maximum attachment. 2. The activity values of both cells tested minocycline were below to the control activity values at all concentrations. 3. The attachment values of both cells tested $TGF-{\beta}1$ were below or similar to control attachment values. On the above the findings, minocycline stimulated the cell attachment of gingival fibroblasts and periodontal ligament cells and $TGF-{\beta}1$ enhances the cell activity of periodontal ligament cells.